Epigenetics - Knowledge

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aversion to this specific odor. They suggested epigenetic changes that increase gene expression, rather than in DNA itself, in a gene, M71, that governs the functioning of an odor receptor in the nose that responds specifically to this cherry blossom smell. There were physical changes that correlated with olfactory (smell) function in the brains of the trained mice and their descendants. Several criticisms were reported, including the study's low statistical power as evidence of some irregularity such as bias in reporting results. Due to limits of sample size, there is a probability that an effect will not be demonstrated to within statistical significance even if it exists. The criticism suggested that the probability that all the experiments reported would show positive results if an identical protocol was followed, assuming the claimed effects exist, is merely 0.4%. The authors also did not indicate which mice were siblings, and treated all of the mice as statistically independent. The original researchers pointed out negative results in the paper's appendix that the criticism omitted in its calculations, and undertook to track which mice were siblings in the future.

1455:(NHEJ) repair of a double-strand break can cause a small number of demethylations of pre-existing cytosine DNA methylations downstream of the repaired double-strand break. Further work by Allen et al. showed that NHEJ of a DNA double-strand break in a cell could give rise to some progeny cells having repressed expression of the gene harboring the initial double-strand break and some progeny having high expression of that gene due to epigenetic alterations associated with NHEJ repair. The frequency of epigenetic alterations causing repression of a gene after an NHEJ repair of a DNA double-strand break in that gene may be about 0.9%. 645: 599: 1249: 1945:, but mammals are not able to respond to loss of some tissues, for example, the inability to regenerate limbs, which some other animals are capable of. Epigenetic modifications regulate the transition from neural stem cells to glial progenitor cells (for example, differentiation into oligodendrocytes is regulated by the deacetylation and methylation of histones). Unlike animals, plant cells do not terminally differentiate, remaining totipotent with the ability to give rise to a new individual plant. While plants do utilize many of the same epigenetic mechanisms as animals, such as 1440:

break. When the chromosome is replicated, this gives rise to one daughter chromosome that is heavily methylated downstream of the previous break site and one that is unmethylated in the region both upstream and downstream of the previous break site. With respect to the gene that was broken by the double-strand break, half of the progeny cells express that gene at a high level and in the other half of the progeny cells expression of that gene is repressed. When clones of these cells were maintained for three years, the new methylation patterns were maintained over that time period.

1674: 777:, and therefore is often referred to as the 'maintenance' methyltransferase. DNMT1 is essential for proper embryonic development, imprinting and X-inactivation. To emphasize the difference of this molecular mechanism of inheritance from the canonical Watson-Crick base-pairing mechanism of transmission of genetic information, the term 'Epigenetic templating' was introduced. Furthermore, in addition to the maintenance and transmission of methylated DNA states, the same principle could work in the maintenance and transmission of histone modifications and even cytoplasmic ( 1761:

later in the hippocampus region of the mouse brain there are 675 demethylated genes and 613 hypermethylated genes. However, memories do not remain in the hippocampus, but after four or five weeks the memories are stored in the anterior cingulate cortex. In the studies on mice after CFC, Halder et al. showed that four weeks after CFC there were at least 1,000 differentially methylated genes and more than 1,000 differentially expressed genes in the anterior cingulate cortex, while at the same time the altered methylations in the hippocampus were reversed.

1737: 2118: 1780:. Roughly 2,500 mRNAs may be localized to the dendrites of hippocampal pyramidal neurons and perhaps 450 transcripts are in excitatory presynaptic nerve terminals (dendritic spines). The altered assortments of transcripts (dependent on epigenetic alterations in the neuron nucleus) have different sensitivities in response to signals, which is the basis of altered synaptic plasticity. Altered synaptic plasticity is often considered the neurochemical foundation of learning and memory. 2231:. In the case of humans with different environmental exposures, monozygotic (identical) twins were epigenetically indistinguishable during their early years, while older twins had remarkable differences in the overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation. The twin pairs who had spent less of their lifetime together and/or had greater differences in their medical histories were those who showed the largest differences in their levels of 2380:, male-induced maternal effects such as the attraction of differential mate quality, and maternal as well as paternal age, and offspring gender could all possibly influence whether a germline epimutation is ultimately expressed in offspring and the degree to which intergenerational inheritance remains stable throughout posterity. However, whether and to what extent epigenetic effects can be transmitted across generations remains unclear, particularly in humans. 29: 15228: 13862: 443: 2605: 216: 15240: 1588:, genetically identical cells show heritable differences in the patterns of ciliary rows on their cell surface. Experimentally altered patterns can be transmitted to daughter cells. It seems existing structures act as templates for new structures. The mechanisms of such inheritance are unclear, but reasons exist to assume that multicellular organisms also use existing cell structures to assemble new ones. 1600:. Nucleosome position is not random, and determine the accessibility of DNA to regulatory proteins. Promoters active in different tissues have been shown to have different nucleosome positioning features. This determines differences in gene expression and cell differentiation. It has been shown that at least some nucleosomes are retained in sperm cells (where most but not all histones are replaced by 2619: 2192:(the pneumococcus) that allows the bacterium to randomly change its characteristics into six alternative states that could pave the way to improved vaccines. Each form is randomly generated by a phase variable methylation system. The ability of the pneumococcus to cause deadly infections is different in each of these six states. Similar systems exist in other bacterial genera. In 1292:(OGG1) is the primary enzyme responsible for the excision of the oxidized guanine during DNA repair. OGG1 finds and binds to an 8-OHdG within a few seconds. However, OGG1 does not immediately excise 8-OHdG. In HeLa cells half maximum removal of 8-OHdG occurs in 30 minutes, and in irradiated mice, the 8-OHdGs induced in the mouse liver are removed with a half-life of 11 minutes. 439:

Therefore, the word "epigenetics" is sometimes used as a synonym for these processes. However, this can be misleading. Chromatin remodeling is not always inherited, and not all epigenetic inheritance involves chromatin remodeling. In 2019, a further lysine modification appeared in the scientific literature linking epigenetics modification to cell metabolism, i.e. lactylation

1143:). These damages are largely repaired, however, epigenetic changes can still remain at the site of DNA repair. In particular, a double strand break in DNA can initiate unprogrammed epigenetic gene silencing both by causing DNA methylation as well as by promoting silencing types of histone modifications (chromatin remodeling - see next section). In addition, the enzyme 3354:: "the theory that the germ is brought into existence (by successive accretions), and not merely developed, in the process of reproduction. The opposite theory was formerly known as the 'theory of evolution'; to avoid the ambiguity of this name, it is now spoken of chiefly as the 'theory of preformation', sometimes as that of 'encasement' or 'emboîtement'." 1558:, allow sequencing of native DNA. Native (=unamplified) DNA retains the epigenetic modifications which would otherwise be lost during the amplification step. Nanopore basecaller models can distinguish between the signals obtained for epigenetically modified bases and unaltered based and provide an epigenetic profile in addition to the sequencing result. 388:(in the progeny of cells or of individuals) and also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable." In 2008, a consensus definition of the epigenetic trait, a "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence," was made at a 475:

histones may be carried into each new copy of the DNA. Once there, these histones may act as templates, initiating the surrounding new histones to be shaped in the new manner. By altering the shape of the histones around them, these modified histones would ensure that a lineage-specific transcription program is maintained after cell division.

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and 3,432 regions for DNMT3B. When DNMT3A2 is newly induced as an IEG (when neurons are activated), many new cytosine methylations occur, presumably in the target regions of DNMT3A2. Oliviera et al. found that the neuronal activity-inducible IEG levels of Dnmt3a2 in the hippocampus determined the ability to form long-term memories.

1015:, prions are more loosely defined by their ability to catalytically convert other native state versions of the same protein to an infectious conformational state. It is in this latter sense that they can be viewed as epigenetic agents capable of inducing a phenotypic change without a modification of the genome. 2136:, it plays a different role in bacteria. Most importantly, eukaryotes use epigenetic mechanisms primarily to regulate gene expression which bacteria rarely do. However, bacteria make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions. Bacteria also use DNA 591:) that have a higher affinity for 5-methylcytosine than for cytosine. If this enzyme reaches a "hemimethylated" portion of DNA (where 5-methylcytosine is in only one of the two DNA strands) the enzyme will methylate the other half. However, it is now known that DNMT1 physically interacts with the protein 2532:

in whole blood. Nuclear factor (NF)-κB inhibitor ε (NFKBIE) directly inhibits NF-κB1 activity and is significantly co-expressed with NF-κB1, also, it is associated with rheumatoid arthritis. Colocalization analysis supports that variants for the majority of the CpG sites in SNP rs730775 cause genetic

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encodes a protein with tyrosine phosphatase activity, which has been previously linked to advanced neoplasia. SNP rs7115089 was identified as influencing DNA methylation and expression of this locus, as well as and Body Mass Index (BMI). In fact, SNP rs7115089 is strongly associated with BMI and with

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Controversial results from one study suggested that traumatic experiences might produce an epigenetic signal that is capable of being passed to future generations. Mice were trained, using foot shocks, to fear a cherry blossom odor. The investigators reported that the mouse offspring had an increased

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Methylation is a widely characterized mechanism of genetic regulation that can determine biological traits. However, strong experimental evidences correlate methylation patterns in SNPs as an important additional feature for the classical activation/inhibition epigenetic dogma. Molecular interaction

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A more recent study, where 114 monozygotic twins and 80 dizygotic twins were analyzed for the DNA methylation status of around 6000 unique genomic regions, concluded that epigenetic similarity at the time of blastocyst splitting may also contribute to phenotypic similarities in monozygotic co-twins.

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Numerous investigations have demonstrated the pivotal involvement of long non-coding RNAs (lncRNAs) in the regulation of gene expression and chromosomal modifications, thereby exerting significant control over cellular differentiation. These long non-coding RNAs also contribute to genomic imprinting

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that range in size from 17 to 25 nucleotides. miRNAs regulate a large variety of biological functions in plants and animals. So far, in 2013, about 2000 miRNAs have been discovered in humans and these can be found online in a miRNA database. Each miRNA expressed in a cell may target about 100 to 200

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It has been shown that the histone lysine methyltransferase (KMT) is responsible for this methylation activity in the pattern of histones H3 & H4. This enzyme utilizes a catalytically active site called the SET domain (Suppressor of variegation, Enhancer of Zeste, Trithorax). The SET domain is a

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One mode of thinking is that this tendency of acetylation to be associated with "active" transcription is biophysical in nature. Because it normally has a positively charged nitrogen at its end, lysine can bind the negatively charged phosphates of the DNA backbone. The acetylation event converts the

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modification of either DNA (e.g. cytosine methylation and hydroxymethylation) or of histone proteins (e.g. lysine acetylation, lysine and arginine methylation, serine and threonine phosphorylation, and lysine ubiquitination and sumoylation) play central roles in many types of epigenetic inheritance.

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In the original sense of this definition, epigenetics referred to all molecular pathways modulating the expression of a genotype into a particular phenotype. Over the following years, with the rapid growth of genetics, the meaning of the word has gradually narrowed. Epigenetics has been defined and

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Various pharmacological agents are applied for the production of induced pluripotent stem cells (iPSC) or maintain the embryonic stem cell (ESC) phenotypic via epigenetic approach. Adult stem cells like bone marrow stem cells have also shown a potential to differentiate into cardiac competent cells

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has been noted to occur in preclinical studies. However, robust evidence in support of the persistence of epigenetic effects across multiple generations has yet to be established in humans; for example, an epigenetic effect of prenatal exposure to smoking that is observed in great-grandchildren who

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repositioning, is very important in the development of multicellular eukaryotic organisms. The genome sequence is static (with some notable exceptions), but cells differentiate into many different types, which perform different functions, and respond differently to the environment and intercellular

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in or near the promoters of genes. As shown by Manzo et al., these three DNA methyltransferases differ in their genomic binding locations and DNA methylation activity at different regulatory sites. Manzo et al. located 3,970 genome regions exclusively enriched for DNMT3A1, 3,838 regions for DNMT3A2

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gene. Oxidative DNA damage from bromate modulated the DNA methylation pattern (caused epigenetic alterations) at CpG sites within the region of DNA studied. In untreated cells, CpGs located at −189, −134, −29, −19, +16, and +19 of the BRCA1 gene had methylated cytosines (where numbering is from the

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Differing histone modifications are likely to function in differing ways; acetylation at one position is likely to function differently from acetylation at another position. Also, multiple modifications may occur at the same time, and these modifications may work together to change the behavior of

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mortality in the grandchildren increased, suggesting that this was a transgenerational epigenetic inheritance. The opposite effect was observed for females – the paternal (but not maternal) granddaughters of women who experienced famine while in the womb (and therefore while their eggs were being

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Dizygotic (fraternal) and monozygotic (identical) twins show evidence of epigenetic influence in humans. DNA sequence differences that would be abundant in a singleton-based study do not interfere with the analysis. Environmental differences can produce long-term epigenetic effects, and different

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proteins may be modified, causing activation or silencing. This mechanism enables differentiated cells in a multicellular organism to express only the genes that are necessary for their own activity. Epigenetic changes are preserved when cells divide. Most epigenetic changes only occur within the

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in 1965 and 1971, are the two best studied of this type of prion. Prions can have a phenotypic effect through the sequestration of protein in aggregates, thereby reducing that protein's activity. In PSI+ cells, the loss of the Sup35 protein (which is involved in termination of translation) causes

807:(KDM). This recently identified enzyme has a catalytically active site called the Jumonji domain (JmjC). The demethylation occurs when JmjC utilizes multiple cofactors to hydroxylate the methyl group, thereby removing it. JmjC is capable of demethylating mono-, di-, and tri-methylated substrates. 687:

Another model of epigenetic function is the "trans" model. In this model, changes to the histone tails act indirectly on the DNA. For example, lysine acetylation may create a binding site for chromatin-modifying enzymes (or transcription machinery as well). This chromatin remodeler can then cause

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of the amino acids that make up histone proteins. Histone proteins are made up of long chains of amino acids. If the amino acids that are in the chain are changed, the shape of the histone might be modified. DNA is not completely unwound during replication. It is possible, then, that the modified

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Developmental epigenetics can be divided into predetermined and probabilistic epigenesis. Predetermined epigenesis is a unidirectional movement from structural development in DNA to the functional maturation of the protein. "Predetermined" here means that development is scripted and predictable.

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in the promoter regions of genes, the genes are often repressed, and when newly demethylated cytosines are present the genes may be activated. After CFC, there were 1,048 genes with reduced mRNA expression and 564 genes with upregulated mRNA expression. Similarly, when mice undergo CFC, one hour

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downstream of the repaired double-strand break. The other DNA strand loses methylation at about six CpG sites that were previously methylated downstream of the double-strand break, as well as losing methylation at about five CpG sites that were previously methylated upstream of the double-strand

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Damage to DNA is very common and is constantly being repaired. Epigenetic alterations can accompany DNA repair of oxidative damage or double-strand breaks. In human cells, oxidative DNA damage occurs about 10,000 times a day and DNA double-strand breaks occur about 10 to 50 times a cell cycle in

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Cell plasticity, which is the adaptation of cells to stimuli without changes in their genetic code, requires epigenetic changes. These have been observed in cell plasticity in cancer cells during epithelial-to-mesenchymal transition and also in immune cells, such as macrophages. Interestingly,

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is the term given to epigenetic modifications as they occur as a direct function with age. While age is a known risk factor for many diseases, age-related methylation has been found to occur differentially at specific sites along the genome. Over time, this can result in measurable differences

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PSI is generated by a conformational change of a translation termination factor, which is then inherited by daughter cells. This can provide a survival advantage under adverse conditions, exemplifying epigenetic regulation which enables unicellular organisms to respond rapidly to environmental

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is a prominent model system for understanding the control and function of cytosine methylation. In this organism, DNA methylation is associated with relics of a genome-defense system called RIP (repeat-induced point mutation) and silences gene expression by inhibiting transcription elongation.

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genes in pathogens and are viewed as new targets in the fight against drug-resistant bacteria. They play an important role in many biological processes, binding to mRNA and protein targets in prokaryotes. Their phylogenetic analyses, for example through sRNA–mRNA target interactions or protein

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where they remain unmethylated. Epigenetic changes of this type thus have the potential to direct increased frequencies of permanent genetic mutation. DNA methylation patterns are known to be established and modified in response to environmental factors by a complex interplay of at least three

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recruits HP1 to K9 methylated regions. One example that seems to refute this biophysical model for methylation is that tri-methylation of histone H3 at lysine 4 is strongly associated with (and required for full) transcriptional activation (see top Figure). Tri-methylation, in this case, would

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Methylation sensitive restriction enzymes paired with PCR is a way to evaluate methylation in DNA - specifically the CpG sites. If DNA is methylated, the restriction enzymes will not cleave the strand. Contrarily, if the DNA is not methylated, the enzymes will cleave the strand and it will be

415:" has been used to describe the set of epigenetic features that create different phenotypes in different cells from the same underlying DNA sequence. Taken to its extreme, the "epigenetic code" could represent the total state of the cell, with the position of each molecule accounted for in an 2258:

and histone modifications in a sample of 40 monozygotic twin pairs. In this case, only healthy twin pairs were studied, but a wide range of ages was represented, between 3 and 74 years. One of the major conclusions from this study was that there is an age-dependent accumulation of epigenetic

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gene shows increased correlation with DNA methylation in people with high abundance of CD8+ T cells. SNP rs174548 is strongly associated with concentrations of arachidonic acid and other metabolites in fatty acid metabolism, blood eosinophil counts. and inflammatory diseases such as asthma.

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metabolic changes underly these adaptations, since various metabolites play crucial roles in the chemistry of epigenetic marks. This includes for instance alpha-ketoglutarate, which is required for histone demethylation, and acetyl-Coenzyme A, which is required for histone acetylation.

1994:. Although epigenetics in multicellular organisms is generally thought to be a mechanism involved in differentiation, with epigenetic patterns "reset" when organisms reproduce, there have been some observations of transgenerational epigenetic inheritance (e.g., the phenomenon of 419:, a diagrammatic representation of the gene expression, DNA methylation and histone modification status of a particular genomic region. More typically, the term is used in reference to systematic efforts to measure specific, relevant forms of epigenetic information such as the 358:

The term has also been used, however, to describe processes which have not been demonstrated to be heritable, such as some forms of histone modification. Consequently, there are attempts to redefine "epigenetics" in broader terms that would avoid the constraints of requiring

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for the duration of the cell's life, and may also last for multiple generations, even though they do not involve changes in the underlying DNA sequence of the organism; instead, non-genetic factors cause the organism's genes to behave (or "express themselves") differently.

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they encode. RNA signalling includes differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development. Other epigenetic changes are mediated by the production of

1776:, translation initiation factors and RNA-binding proteins that regulate mRNA function. These neuronal granules are transported from the neuron nucleus and are directed, according to 3′ untranslated regions of the mRNA in the granules (their "zip codes"), to neuronal 7981:

Chaumeil J, Augui S, Chow JC, Heard E (2008). "Combined Immunofluorescence, RNA Fluorescent in Situ Hybridization, and DNA Fluorescent in Situ Hybridization to Study Chromatin Changes, Transcriptional Activity, Nuclear Organization, and X-Chromosome Inactivation".

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Mechanisms of heritability of histone state are not well understood; however, much is known about the mechanism of heritability of DNA methylation state during cell division and differentiation. Heritability of methylation state depends on certain enzymes (such as

922:, that may be repressed by epigenetic methylation. Transcription from methylated CpG islands is strongly and heritably repressed. Other miRNAs are epigenetically regulated by either histone modifications or by combined DNA methylation and histone modification. 9907:

This might suggest that plant cells do not use or require a cellular memory mechanism and just respond to positional information. However, it has been shown that plants do use cellular memory mechanisms mediated by PcG proteins in several processes, ... (p.

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hybridization (FISH) is very important to understand epigenetic mechanisms. FISH can be used to find the location of genes on chromosomes, as well as finding noncoding RNAs. FISH is predominantly used for detecting chromosomal abnormalities in humans.

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Chromatin Immunoprecipitation (ChIP) has helped bridge the gap between DNA and epigenetic interactions. With the use of ChIP, researchers are able to make findings in regards to gene regulation, transcription mechanisms, and chromatin structure.

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region). Bromate treatment-induced oxidation resulted in the loss of cytosine methylation at −189, −134, +16 and +19 while also leading to the formation of new methylation at the CpGs located at −80, −55, −21 and +8 after DNA repair was allowed.

1234:(8-OHdG) in the average mammalian cell DNA. 8-OHdG constitutes about 5% of the oxidative damages commonly present in DNA. The oxidized guanines do not occur randomly among all guanines in DNA. There is a sequence preference for the guanine at a 595:. UHRF1 has been recently recognized as essential for DNMT1-mediated maintenance of DNA methylation. UHRF1 is the protein that specifically recognizes hemi-methylated DNA, therefore bringing DNMT1 to its substrate to maintain DNA methylation. 1191:. In one study, markers for oxidative stress, such as modified nucleotides that can result from DNA damage, were decreased by a 3-week diet supplemented with soy. A decrease in oxidative DNA damage was also observed 2 h after consumption of 766:, DNMT1, DNMT3A, and DNMT3B, the loss of any of which is lethal in mice. DNMT1 is the most abundant methyltransferase in somatic cells, localizes to replication foci, has a 10–40-fold preference for hemimethylated DNA and interacts with the 13249:

Astle WJ, UK Blood Trait GWAS Team, Cambridge BLUEPRINT epigenome (2 December 2016). "A GWAS of 170,000 Individuals Identifies Thousands of Alleles Perturbing Blood Cell Traits, Many of Which Are in Super Enhancers Setting Cell Identity".

1949:, it has been hypothesized that some kinds of plant cells do not use or require "cellular memories", resetting their gene expression patterns using positional information from the environment and surrounding cells to determine their fate. 986:

and the inactivation of the X chromosome. In invertebrates such as social insects of honey bees, long non-coding RNAs are detected as a possible epigenetic mechanism via allele-specific genes underlying aggression via reciprocal crosses.

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at early stages of embryonic development can be quite important for the establishment of epigenetic marks. Congenital genetic disease is well understood and it is clear that epigenetics can play a role, for example, in the case of

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and neuroepigenetic mechanisms and occurs over time from chronically high levels of exposure to an addictive stimulus (e.g., morphine, cocaine, sexual intercourse, gambling). Transgenerational epigenetic inheritance of addictive

1011:. In general, proteins fold into discrete units that perform distinct cellular functions, but some proteins are also capable of forming an infectious conformational state known as a prion. Although often viewed in the context of 574:

appears to partly rely on recognition of histone methylation on the nucleosome present at the DNA site to carry out cytosine methylation on newly synthesized DNA. There is further crosstalk between DNA methylation carried out by

2109:, in which polymerase sensitivity allows for measuring methylation and other modifications as a DNA molecule is being sequenced. Several projects have demonstrated the ability to collect genome-wide epigenetic data in bacteria. 2186:, adenine methylation provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage, transposase activity and regulation of gene expression. There exists a genetic switch controlling 1147:

and its product poly(ADP)-ribose (PAR) accumulate at sites of DNA damage as part of the repair process. This accumulation, in turn, directs recruitment and activation of the chromatin remodeling protein, ALC1, that can cause

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and other transcriptional factors can bind to the DNA and allow transcription to occur. This is the "cis" model of the epigenetic function. In other words, changes to the histone tails have a direct effect on the DNA itself.

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Anderson SJ, Feye KM, Schmidt-McCormack GR, Malovic E, Mlynarczyk GS, Izbicki P, et al. (May 2016). "Off-Target drug effects resulting in altered gene expression events with epigenetic and "Quasi-Epigenetic" origins".

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are incorporated into specific regions of the genome non-randomly. Their differential biochemical characteristics can affect genome functions via their roles in gene regulation, and maintenance of chromosome structures.

3333:"For the purpose of a study of inheritance, the relation between phenotypes and genotypes is, from a wider biological point of view, of crucial importance, since it is the kernel of the whole problem of development." 367:

defined epigenetics as "the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states." This definition would be inclusive of transient modifications associated with

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Areas of the brain important in the formation of memories include the hippocampus, medial prefrontal cortex (mPFC), anterior cingulate cortex and amygdala, as shown in the diagram of the human brain in this section.

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The three-dimensional configuration of the genome (the 3D genome) is complex, dynamic and crucial for regulating genomic function and nuclear processes such as DNA replication, transcription and DNA-damage repair.

1604:). Thus nucleosome positioning is to some degree inheritable. Recent studies have uncovered connections between nucleosome positioning and other epigenetic factors, such as DNA methylation and hydroxymethylation. 6873:

Kikuno N, Shiina H, Urakami S, Kawamoto K, Hirata H, Tanaka Y, et al. (August 2008). "Genistein mediated histone acetylation and demethylation activates tumor suppressor genes in prostate cancer cells".

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In mice with a CRISPR-mediated homology-directed recombination insertion in their genome there were a large number of increased methylations of CpG sites within the double-strand break-associated insertion.

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messenger RNAs(mRNAs) that it downregulates. Most of the downregulation of mRNAs occurs by causing the decay of the targeted mRNA, while some downregulation occurs at the level of translation into protein.

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Knoll JH, Nicholls RD, Magenis RE, Graham JM, Lalande M, Latt SA (February 1989). "Angelman and Prader–Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion".

724:, although the idea that histone state can be read linearly as a digital information carrier has been largely debunked. One of the best-understood systems that orchestrate chromatin-based silencing is the 2338:, paternal (but not maternal) grandsons of Swedish men who were exposed during preadolescence to famine in the 19th century were less likely to die of cardiovascular disease. If food was plentiful, then 898:

phenotypes. A smaller quantity of sperm RNA is transmitted from the father, but there is recent evidence that this epigenetic information can lead to visible changes in several generations of offspring.

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proteins in a tightly assembled core region plus up to 30% of each histone remaining in a loosely organized tail (only one tail of each pair is shown). DNA is wrapped around the histone core proteins in

866:). Descendants of the cell in which the gene was turned on will inherit this activity, even if the original stimulus for gene-activation is no longer present. These genes are often turned on or off by 810:

Chromosomal regions can adopt stable and heritable alternative states resulting in bistable gene expression without changes to the DNA sequence. Epigenetic control is often associated with alternative

522:). About 22% of transcription factors are inhibited from binding when the recognition sequence has a methylated cytosine. In addition, presence of methylated cytosines at a promoter region can attract 1756:. Duke et al. found that 24 hours after CFC in rats, in hippocampus neurons, 2,097 genes (9.17% of the genes in the rat genome) had altered methylation. When newly methylated cytosines are present in 1721:. EGR1 protein binds to DNA at its binding motifs, 5′-GCGTGGGCG-3′ or 5′-GCGGGGGCGG-3', and there are about 12,000 genome locations at which EGR1 protein can bind. EGR1 protein binds to DNA in gene 466:

proteins with which it associates. If the way that DNA is wrapped around the histones changes, gene expression can change as well. Chromatin remodeling is accomplished through two main mechanisms:

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state approach to the study of cell-fate. Cell-fate determination is predicted to exhibit certain dynamics, such as attractor-convergence (the attractor can be an equilibrium point, limit cycle or

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Yuan TF, Li A, Sun X, Ouyang H, Campos C, Rocha NB, et al. (November 2016). "Transgenerational Inheritance of Paternal Neurobehavioral Phenotypes: Stress, Addiction, Ageing and Metabolism".

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of the double-strand break, the involvement of DNMT1 causes the two repaired strands of DNA to have different levels of methylated cytosines. One strand becomes frequently methylated at about 21

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data, supported by colocalization analyses, identify multiple nuclear regulatory pathways, linking sequence variation to disturbances in DNA methylation and molecular and phenotypic variation.

2002:). Although most of these multigenerational epigenetic traits are gradually lost over several generations, the possibility remains that multigenerational epigenetics could be another aspect to 1764:

The epigenetic alteration of methylation after a new memory is established creates a different pool of nuclear mRNAs. As reviewed by Bernstein, the epigenetically determined new mix of nuclear

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Bisulfite sequencing is another way to evaluate DNA methylation. Cytosine will be changed to uracil from being treated with sodium bisulfite, whereas methylated cytosines will not be affected.

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changes to the state of the chromatin. Indeed, a bromodomain – a protein domain that specifically binds acetyl-lysine – is found in many enzymes that help activate transcription, including the

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Although histone modifications occur throughout the entire sequence, the unstructured N-termini of histones (called histone tails) are particularly highly modified. These modifications include

628:. The lysines (K) are designated with a number showing their position as, for instance (K4), indicating lysine as the 4th amino acid from the amino (N) end of the tail in the histone protein. 1222:). The selective advantage of DNA repair is to allow the cell to survive in the face of DNA damage. The selective advantage of epigenetic alterations that occur with DNA repair is not clear. 9057:

Halder R, Hennion M, Vidal RO, Shomroni O, Rahman RU, Rajput A, et al. (January 2016). "DNA methylation changes in plasticity genes accompany the formation and maintenance of memory".

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Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. (February 2005). "Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs".

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Some human disorders are associated with genomic imprinting, a phenomenon in mammals where the father and mother contribute different epigenetic patterns for specific genomic loci in their

384:"Roadmap Epigenomics Project", which ran from 2008 to 2017, uses the following definition: "For purposes of this program, epigenetics refers to both heritable changes in gene activity and 679:

positively charged amine group on the side chain into a neutral amide linkage. This removes the positive charge, thus loosening the DNA from the histone. When this occurs, complexes like

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may concurrently influence genetic and epigenetic inheritance using similar molecular mechanisms, and may be a point of crosstalk between these conceptually compartmentalized processes.

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expression is an indicator of caloric restriction that may drive programmed susceptibility to obesity and it is associated with other measures of adiposity in human peripherical blood.

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Zaidi SK, Lian JB, van Wijnen A, Stein JL, Stein GS (2017). "Mitotic Gene Bookmarking: An Epigenetic Mechanism for Coordination of Lineage Commitment, Cell Identity and Cell Growth".

318:. Waddington suggested visualising increasing irreversibility of cell type differentiation as ridges rising between the valleys where the marbles (analogous to cells) are travelling. 2254:

study, which denotes technology that looks at extensive genetic markers, focused on epigenetic differences between monozygotic twins to compare global and locus-specific changes in

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localizing to oxidized guanines. Polymerase beta is the main human polymerase in short-patch BER of oxidative DNA damage. Jiang et al. also found that polymerase beta recruited the

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Kropat C, Mueller D, Boettler U, Zimmermann K, Heiss EH, Dirsch VM, et al. (March 2013). "Modulation of Nrf2-dependent gene transcription by bilberry anthocyanins in vivo".

1314:

for six hours, 8-OHdG increased about 3.5-fold in DNA and this caused about 80% demethylation of the 5-methylcytosines in the genome. Demethylation of CpGs in a gene promoter by

13950: 12951:"Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis" 7483:"Oxidative DNA Damage Modulates DNA Methylation Pattern in Human Breast Cancer 1 (BRCA1) Gene via the Crosstalk between DNA Polymerase β and a de novo DNA Methyltransferase" 519: 118:

sequence. Further, non-coding RNA sequences have been shown to play a key role in the regulation of gene expression. Gene expression can be controlled through the action of

1068:. Moreover, if gene inactivation occurs in a sperm or egg cell that results in fertilization, this epigenetic modification may also be transferred to the next generation. 10335:

Danchin É, Charmantier A, Champagne FA, Mesoudi A, Pujol B, Blanchet S (June 2011). "Beyond DNA: integrating inclusive inheritance into an extended theory of evolution".

2801:

today is generally accepted as 'the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence.'

712:

130-amino acid sequence involved in modulating gene activities. This domain has been demonstrated to bind to the histone tail and causes the methylation of the histone.

918:

It appears that about 60% of human protein coding genes are regulated by miRNAs. Many miRNAs are epigenetically regulated. About 50% of miRNA genes are associated with

13002:"Blood cell transcriptomic-based early biomarkers of adverse programming effects of gestational calorie restriction and their reversibility by leptin supplementation" 5919:"The spontaneous appearance rate of the yeast prion [PSI+] and its implications for the evolution of the evolvability properties of the [PSI+] system" 1693:

in neurons of the hippocampus and the medial prefrontal cortex (mPFC). These double-strand breaks are at specific locations that allow activation of transcription of

1670:

An event can set off a chain of reactions that result in altered methylations of a large set of genes in neurons, which give a representation of the event, a memory.

795:

RNA methylation of N6-methyladenosine (m6A) as the most abundant eukaryotic RNA modification has recently been recognized as an important gene regulatory mechanism.

2557:

Interaction results indicated a correlation between rs174548 and asthma, providing new insights about fatty acid metabolism in CD8+ T cells with immune phenotypes.

7701:"Rapid and transient recruitment of DNMT1 to DNA double-strand breaks is mediated by its interaction with multiple components of the DNA damage response machinery" 2041:). Thomas Dickins and Qazi Rahman state that epigenetic mechanisms such as DNA methylation and histone modification are genetically inherited under the control of 1059:

Epigenetic changes modify the activation of certain genes, but not the genetic code sequence of DNA. The microstructure (not code) of DNA itself or the associated

13358:

Haque FN, Gottesman II, Wong AH (May 2009). "Not really identical: epigenetic differences in monozygotic twins and implications for twin studies in psychiatry".

2063:

In plants, heritable DNA methylation mutations are 100,000 times more likely to occur compared to DNA mutations. An epigenetically inherited element such as the

1838: 298:

and their role in heredity was not known. He used it instead as a conceptual model of how genetic components might interact with their surroundings to produce a

703:) (see bottom Figure). It has been determined that a chromodomain (a domain that specifically binds methyl-lysine) in the transcriptionally repressive protein 8956:"Fear memory formation can affect a different memory: fear conditioning affects the extinction, but not retrieval, of conditioned taste aversion (CTA) memory" 6961:

Djuric Z, Chen G, Doerge DR, Heilbrun LK, Kucuk O (October 2001). "Effect of soy isoflavone supplementation on markers of oxidative stress in men and women".

2067:

system can act as a "stop-gap", good enough for short-term adaptation that allows the lineage to survive for long enough for mutation and/or recombination to

13700: 2653: 9100:

Frankland PW, Bontempi B, Talton LE, Kaczmarek L, Silva AJ (May 2004). "The involvement of the anterior cingulate cortex in remote contextual fear memory".

13153:"Genome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium" 1303:

to the 8-OHdG lesion (see Figure). This allows TET1 to demethylate an adjacent methylated cytosine. Demethylation of cytosine is an epigenetic alteration.

1175:

Foods are known to alter the epigenetics of rats on different diets. Some food components epigenetically increase the levels of DNA repair enzymes such as

490:. 5-Methylcytosine performs much like a regular cytosine, pairing with a guanine in double-stranded DNA. However, when methylated cytosines are present in 340:

defined in 1990 epigenetics as "the study of the mechanisms of temporal and spatial control of gene activity during the development of complex organisms."

2466: 1139:

DNA damage can also cause epigenetic changes. DNA damage is very frequent, occurring on average about 60,000 times a day per cell of the human body (see

1064:

course of one individual organism's lifetime; however, these epigenetic changes can be transmitted to the organism's offspring through a process called

9237:

Braga DL, Mousovich-Neto F, Tonon-da-Silva G, Salgueiro WG, Mori MA (August 2020). "Epigenetic changes during ageing and their underlying mechanisms".

2293:. These are normal genetic diseases caused by gene deletions or inactivation of the genes but are unusually common because individuals are essentially 1152:

remodeling. Nucleosome remodeling has been found to cause, for instance, epigenetic silencing of DNA repair gene MLH1. DNA damaging chemicals, such as

1401:

protein DNMT3b to BER repair sites. They then evaluated the methylation pattern at the single nucleotide level in a small region of DNA including the

10811:

Davies, Hazel (2008). Do Butterflies Bite?: Fascinating Answers to Questions about Butterflies and Moths (Animals Q&A). Rutgers University Press.

7134:"Mapping structurally defined guanine oxidation products along DNA duplexes: influence of local sequence context and endogenous cytosine methylation" 2413:

The two forms of heritable information, namely genetic and epigenetic, are collectively called dual inheritance. Members of the APOBEC/AID family of

2052:

Two important ways in which epigenetic inheritance can differ from traditional genetic inheritance, with important consequences for evolution, are:

1933:

activate or silence genes in an epigenetically heritable fashion, giving cells a memory. In mammals, most cells terminally differentiate, with only

12685: 2643: 1374:) to sites of some kinds of oxidative DNA damage. This could cause increased methylation of cytosines (epigenetic alterations) at these locations. 1038:

in other genes. The ability of Sup35 to form prions may be a conserved trait. It could confer an adaptive advantage by giving cells the ability to

11453:

Kaminsky ZA, Tang T, Wang SC, Ptak C, Oh GH, Wong AH, et al. (February 2009). "DNA methylation profiles in monozygotic and dizygotic twins".

9868: 5551:

Ruffo, Paola, et al. "Long-noncoding RNAs as epigenetic regulators in neurodegenerative diseases." Neural Regeneration Research 18.6 (2023): 1243.

1021:

are considered by some to be epigenetic because the infectious phenotype caused by the prion can be inherited without modification of the genome.

9599:

Ekstrand B, Scheers N, Rasmussen MK, Young JF, Ross AB, Landberg R (May 2021). "Brain foods - the role of diet in brain performance and health".

4549:

Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF (September 1997). "Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1".

2247:

developmental monozygotic twin subtypes may be different with respect to their susceptibility to be discordant from an epigenetic point of view.

376:

phases as well as stable changes maintained across multiple cell generations, but exclude others such as templating of membrane architecture and

13481: 1921:

Probabilistic epigenesis on the other hand is a bidirectional structure-function development with experiences and external molding development.

13057:

Okada Y (November 2014). "From the era of genome analysis to the era of genomic drug discovery: a pioneering example of rheumatoid arthritis".

837:

Sometimes a gene, after being turned on, transcribes a product that (directly or indirectly) maintains the activity of that gene. For example,

7186:

Zhou X, Zhuang Z, Wang W, He L, Wu H, Cao Y, et al. (September 2016). "OGG1 is essential in oxidative stress-induced DNA demethylation".

1960:, which affects their fur color, weight, and propensity to develop cancer. Ongoing research is focused on exploring the impact of other known 814:

of histones. The stability and heritability of states of larger chromosomal regions are suggested to involve positive feedback where modified

15278: 6926: 3096: 699:

as well. Methylation of lysine 9 of histone H3 has long been associated with constitutively transcriptionally silent chromatin (constitutive

671:, ribosylation and citrullination. Acetylation is the most highly studied of these modifications. For example, acetylation of the K14 and K9 11764: 11312:"Epigenomic characterization of Clostridioides difficile finds a conserved DNA methyltransferase that mediates sporulation and pathogenesis" 9823:

Griesemer J, Haber MH, Yamashita G, Gannett L (March 2005). "Critical Notice: Cycles of Contingency – Developmental Systems and Evolution".

8215:

Simpson JT, Workman RE, Zuzarte PC, David M, Dursi LJ, Timp W (April 2017). "Detecting DNA cytosine methylation using nanopore sequencing".

2331:, and the particular syndrome that will develop depends on whether the mutation is inherited from the child's mother or from their father. 1858: 1733:

to an association, and brings TET1 to about 600 locations on the genome where TET1 can then demethylate and activate the associated genes.

10738: 2301:, and therefore a single gene knock out is sufficient to cause the disease, where most cases would require both copies to be knocked out. 14806: 8802:

Oliveira AM, Hemstedt TJ, Bading H (July 2012). "Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities".

5563:"Examining parent-of-origin effects on transcription and RNA methylation in mediating aggressive behavior in honey bees (Apis mellifera)" 1230:

In the steady state (with endogenous damages occurring and being repaired), there are about 2,400 oxidatively damaged guanines that form

380:

unless they impinge on chromosome function. Such redefinitions however are not universally accepted and are still subject to debate. The

10241: 10110:"Fearful Memories Passed Down to Mouse Descendants: Genetic imprint from traumatic experiences carries through at least two generations" 583:

and histone methylation so that there is a correlation between the genome-wide distribution of DNA methylation and histone methylation.

13725: 7750:"DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism" 7085:"A reliable assessment of 8-oxo-2-deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA" 675:

of the tail of histone H3 by histone acetyltransferase enzymes (HATs) is generally related to transcriptional competence (see Figure).

12093:

Biliński P, Wojtyła A, Kapka-Skrzypczak L, Chwedorowicz R, Cyranka M, Studziński T (2012). "Epigenetic regulation in drug addiction".

3187:

1653, p. 272. It is explained to mean ‘partium super-exorientium additamentum’, ‘the additament of parts budding one out of another’."

964:

are small (50–250 nucleotides), highly structured, non-coding RNA fragments found in bacteria. They control gene expression including

15744: 13898: 5139:

Wang Z, Yao H, Lin S, Zhu X, Shen Z, Lu G, et al. (April 2013). "Transcriptional and epigenetic regulation of human microRNAs".

2689: 227:

as a "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence" was formulated at a

13102:"FADS1-FADS2 genetic polymorphisms are associated with fatty acid metabolism through changes in DNA methylation and gene expression" 818:

recruit enzymes that similarly modify nearby nucleosomes. A simplified stochastic model for this type of epigenetics is found here.

12222:

Chahwan R, Wontakal SN, Roa S (October 2010). "Crosstalk between genetic and epigenetic information through cytosine deamination".

9423:

Grigorenko EL, Kornilov SA, Naumova OY (November 2016). "Epigenetic regulation of cognition: A circumscribed review of the field".

7650:"Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island" 6464:"Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island" 2739: 2079: 1985: 1909: 1065: 208:

has a generic meaning of "extra growth" that has been used in English since the 17th century. In scientific publications, the term

4452:"The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors" 13847: 11881:

Coplan J, Chanatry ST, Rosenblum LA (2017). "Persistence of Early-Life Stress on the Epigenome: Nonhuman Primate Observations☆".

1176: 1012: 12628:

Shin H, Choi WL, Lim JY, Huh JH (March 2022). "Epigenome editing: targeted manipulation of epigenetic modifications in plants".

1865:

seem "central to building an 'epigenetic memory' to influence long-term brain function and behavior" and may even be heritable.

14775: 4407:

Li E, Bestor TH, Jaenisch R (June 1992). "Targeted mutation of the DNA methyltransferase gene results in embryonic lethality".

510:

excluding the transcription start site) expression of the gene is often enhanced. Transcription of a gene usually depends on a

13335: 11098:"Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing" 5461:"Analysis of the small RNA transcriptional response in multidrug-resistant Staphylococcus aureus after antimicrobial exposure" 5112: 2102:

stress. Prions can be viewed as epigenetic agents capable of inducing a phenotypic change without modification of the genome.

720:. The idea that multiple dynamic modifications regulate gene transcription in a systematic and reproducible way is called the 15739: 14066: 13487: 12804:"Meta-analysis of genome-wide association studies for height and body mass index in ~700000 individuals of European ancestry" 12745:"Protein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis" 11928: 11359:

Chahwan R, Wontakal SN, Roa S (March 2011). "The multidimensional nature of epigenetic information and its role in disease".

10882: 10289: 10264: 8337: 8312: 8275: 7999: 6134: 5770:

True HL, Lindquist SL (September 2000). "A yeast prion provides a mechanism for genetic variation and phenotypic diversity".

5046: 4288: 3604: 3500:

Rabajante JF, Babierra AL (March 2015). "Branching and oscillations in the epigenetic landscape of cell-fate determination".

3373: 3209: 1942: 10739:"Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution" 773:

By preferentially modifying hemimethylated DNA, DNMT1 transfers patterns of methylation to a newly synthesized strand after

15543: 13705: 6362:"Radiation-induced alterations in histone modification patterns and their potential impact on short-term radiation effects" 4224:"Relationship between histone H3 lysine 9 methylation, transcription repression, and heterochromatin protein 1 recruitment" 2106: 845:

enhance the transcription of many liver-specific and muscle-specific genes, respectively, including their own, through the

12359:"Inhibition of G9a Histone Methyltransferase Converts Bone Marrow Mesenchymal Stem Cells to Cardiac Competent Progenitors" 8330:

Cycles of Contingency: Developmental Systems and Evolution (Life and Mind: Philosophical Issues in Biology and Psychology)

4962: 2817: 534:

complexes, which leads to gene silencing. In addition, another covalent modification involving methylated cytosine is its

14831: 14740: 13549: 11615: 8027: 2674: 2198: 1245:

and where the cytosine is methylated (5-mCpG)). A 5-mCpG site has the lowest ionization potential for guanine oxidation.

603:

Some acetylations and some methylations of lysines (symbol K) are activation signals for transcription when present on a

12853:"Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry" 9684: 6665:"Epigenetic factors in cancer risk: effect of chemical carcinogens on global DNA methylation pattern in human TK6 cells" 3280: 2021:

and Étienne Danchin have argued that these effects may require enhancements to the standard conceptual framework of the

1952:

Epigenetic changes can occur in response to environmental exposure – for example, maternal dietary supplementation with

554:

There is frequently a reciprocal relationship between DNA methylation and histone lysine methylation. For instance, the

15150: 14853: 14585: 14313: 13930: 13720: 13514: 12686:"Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function" 10998:"Comprehensive methylome characterization of Mycoplasma genitalium and Mycoplasma pneumoniae at single-base resolution" 10900:"Modeling kinetic rate variation in third generation DNA sequencing data to detect putative modifications to DNA bases" 3875:

Greenberg MV, Bourc'his D (October 2019). "The diverse roles of DNA methylation in mammalian development and disease".

1655: 1242: 767: 10128: 10012:"The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome" 4680:"Analysis of human histone H2AZ deposition in vivo argues against its direct role in epigenetic templating mechanisms" 2361:

can alter glutamate receptor activity and the action of cyclosporine on multiple transcription factors. Additionally,

2144:

methylation) as an epigenetic signal. DNA adenine methylation is important in bacteria virulence in organisms such as

321:

In recent times, Waddington's notion of the epigenetic landscape has been rigorously formalized in the context of the

212:

started to appear in the 1930s (see Fig. on the right). However, its contemporary meaning emerged only in the 1990s.

15271: 15142: 15082: 14285: 14038: 11898: 9532: 2082:

phenomena have been reported in a wide range of organisms, including prokaryotes, plants, and animals. For instance,

1480: 821:

It has been suggested that chromatin-based transcriptional regulation could be mediated by the effect of small RNAs.

76:

mechanism of inheritance. Epigenetics usually involves a change that is not erased by cell division, and affects the

13446: 10688:"Complex adaptations can drive the evolution of the capacitor [PSI], even with realistic rates of yeast sex" 9468:"Epigenetics of the developing and aging brain: Mechanisms that regulate onset and outcomes of brain reorganization" 2259:

differences between the two siblings of twin pairs. This accumulation suggests the existence of epigenetic "drift".

14542: 14328: 14323: 8355:"Tissue-specific profiling reveals distinctive regulatory architectures for ubiquitous, germline and somatic genes" 1884: 1862: 1281: 1219: 1140: 462:. One way that genes are regulated is through the remodeling of chromatin. Chromatin is the complex of DNA and the 15204: 15087: 14799: 14192: 14136: 5437: 2669: 2328: 2046: 2026: 2022: 1826:

are dynamic and reversible. Epigenetic regulation impacts neuronal action, affecting learning, memory, and other

637: 471: 6724:"Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition" 3438:

Alvarez-Buylla ER, Chaos A, Aldana M, Benítez M, Cortes-Poza Y, Espinosa-Soto C, et al. (3 November 2008).

1280:

targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits

14131: 10996:

Lluch-Senar M, Luong K, Lloréns-Rico V, Delgado J, Fang G, Spittle K, et al. (2013). Richardson PM (ed.).

8395:"Nucleosome repositioning links DNA (de)methylation and differential CTCF binding during stem cell development" 5508: 3918:

Spitz F, Furlong EE (September 2012). "Transcription factors: from enhancer binding to developmental control".

2505:

as a potential mediator of adiposity and cardiometabolic disease. In addition, animal models demonstrated that

1744:

The DNA methyltransferases DNMT3A1, DNMT3A2 and DNMT3B can all methylate cytosines (see image this section) at

231:

meeting in 2008, although alternate definitions that include non-heritable traits are still being used widely.

14719: 11717:

A person's paternal grandson is the son of a son of that person; a maternal grandson is the son of a daughter.

8058:"Improved quantification of DNA methylation using methylation-sensitive restriction enzymes and real-time PCR" 1818:

are important for various higher cognitive functions. Dysregulation of epigenetic mechanisms is implicated in

1793: 15209: 15199: 15186: 14570: 14219: 14150: 13891: 5526: 4361:

Slotkin RK, Martienssen R (April 2007). "Transposable elements and the epigenetic regulation of the genome".

1468: 1096: 389: 381: 228: 77: 10282:

Evolution in four dimensions: genetic, epigenetic, behavioral, and symbolic variation in the history of life

9515:

Streifer M, Gore AC (2021). "Epigenetics, estrogenic endocrine-disrupting chemicals (EDCs), and the brain".

7858:"Non-homologous end joining induced alterations in DNA methylation: A source of permanent epigenetic change" 7382:"Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins" 2552:

Fatty acid desaturase 1 (FADS1) is a key enzyme in the metabolism of fatty acids. Moreover, rs174548 in the

1370:

for 30 minutes causes the mismatch repair protein heterodimer MSH2-MSH6 to recruit DNA methyltransferase 1 (

692:

complex. It may be that acetylation acts in this and the previous way to aid in transcriptional activation.

15264: 14826: 13955: 13806: 12949:

Richardson TG, Sanderson E, Palmer TM, Ala-Korpela M, Ference BA, Davey Smith G, et al. (March 2020).

11842:"Understanding Epigenetic Effects of Endocrine Disrupting Chemicals: From Mechanisms to Novel Test Methods" 10109: 8158:"RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee" 520:

Gene expression#Enhancers, transcription factors, mediator complex and DNA loops in mammalian transcription

11567:"Potential Diagnostic and Prognostic Biomarkers of Epigenetic Drift within the Cardiovascular Compartment" 9761: 9151:

Barter JD, Foster TC (October 2018). "Aging in the Brain: New Roles of Epigenetics in Cognitive Decline".

7272:"Lost in the Crowd: How Does Human 8-Oxoguanine DNA Glycosylase 1 (OGG1) Find 8-Oxoguanine in the Genome?" 7033:"Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment" 543: 14537: 9685:"New discovery: Synapse hiding in the mice brain may advance our understanding of neuronal communication" 9194:

Harman MF, Martín MG (February 2020). "Epigenetic mechanisms related to cognitive decline during aging".

2709: 2265: 1819: 20: 12902:"Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank" 12721: 2180:, methylation of adenine regulates the cell cycle and couples gene transcription to DNA replication. In 1689:(CFC), one of the earliest events to occur is that more than 100 DNA double-strand breaks are formed by 610:

Some methylations on lysines or arginine (R) are repression signals for transcription when present on a

15232: 14792: 14729: 14595: 14427: 14170: 13554: 13471: 9899: 8105:

Li-Byarlay H, Boncristiani H, Howell G, Herman J, Clark L, Strand MK, et al. (24 September 2020).

7807:"Detection of CRISPR-mediated genome modifications through altered methylation patterns of CpG islands" 3126:

Reik W (May 2007). "Stability and flexibility of epigenetic gene regulation in mammalian development".

2281: 2038: 1844:

Epigenetic mechanisms have been proposed as "a potential molecular mechanism for effects of endogenous

1452: 1269: 1231: 1172:, cause considerable hypomethylation of DNA, some through the activation of oxidative stress pathways. 1144: 804: 12310:"The histone methyltransferase inhibitor BIX01294 enhances the cardiac potential of bone marrow cells" 6317:

Ilnytskyy Y, Kovalchuk O (September 2011). "Non-targeted radiation effects-an epigenetic connection".

2501:

genetic variants linked to other cardiovascular and metabolic traits in GWASs. New studies suggesting

1937:

retaining the ability to differentiate into several cell types ("totipotency" and "multipotency"). In

14422: 13710: 13695: 6824:"The flavoring agent dihydrocoumarin reverses epigenetic silencing and inhibits sirtuin deacetylases" 3350: 3176: 2648: 2324: 2290: 2251: 2228: 1500: 704: 555: 523: 344: 92: 11727:

Pembrey ME, Bygren LO, Kaati G, Edvinsson S, Northstone K, Sjöström M, et al. (February 2006).

10758: 8907:"Isoform-specific localization of DNMT3A regulates DNA methylation fidelity at bivalent CpG islands" 7960: 6722:

Burdge GC, Hoile SP, Uller T, Thomas NA, Gluckman PD, Hanson MA, et al. (2011). Imhof A (ed.).

5966:

Garcia DM, Campbell EA, Jakobson CM, Tsuchiya M, Shaw EA, DiNardo AL, et al. (September 2021).

4501:"A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei" 64: 15770: 14214: 14002: 13915: 13884: 13715: 13534: 13423: 12308:

Mezentseva NV, Yang J, Kaur K, Iaffaldano G, Rémond MC, Eisenberg CA, et al. (February 2013).

10059:

Schulze KV, Bhatt A, Azamian MS, Sundgren NC, Zapata GE, Hernandez P, et al. (November 2019).

7380:

Maeder ML, Angstman JF, Richardson ME, Linder SJ, Cascio VM, Tsai SQ, et al. (December 2013).

6557:"Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler" 2188: 1432: 1047: 1039: 1026: 939: 644: 598: 455: 280: 139: 12573:"Epigenetics: Roles and therapeutic implications of non-coding RNA modifications in human cancers" 10193:"Parental olfactory experience influences behavior and neural structure in subsequent generations" 9922:"Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring" 9564:

Bekdash RA (January 2018). "Choline, the brain and neurodegeneration: insights from epigenetics".

5459:

Howden BP, Beaume M, Harrison PF, Hernandez D, Schrenzel J, Seemann T, et al. (August 2013).

4126:"The interplay between DNA and histone methylation: molecular mechanisms and disease implications" 2086:

will change color through hormone changes in response to experimentation of varying temperatures.

1268:-pG, or 5mCpG. Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming 219:

Number of patent families and non-patent documents with the term "epigenetic*" by publication year

176:, the resulting daughter cells change into all the different cell types in an organism, including 14871: 14663: 14600: 14575: 14458: 14378: 14175: 13992: 13977: 12851:

Pulit SL, Stoneman C, Morris AP, Wood AR, Glastonbury CA, Tyrrell J, et al. (January 2019).

11768: 7805:

Farris MH, Texter PA, Mora AA, Wiles MV, Mac Garrigle EF, Klaus SA, et al. (December 2020).

2986:"The Importance of ncRNAs as Epigenetic Mechanisms in Phenotypic Variation and Organic Evolution" 2724: 2369:

drugs via chronic use can increase the expression of genes associated with addictive phenotypes.

2264:

between biological and chronological age. Epigenetic changes have been found to be reflective of

1854:

could interact with the epigenome to "protect or boost cognitive processes across the lifespan".

1339:

was reduced (an epigenetic alteration) and this allowed about 6.5 fold increase of expression of

1100: 420: 311: 15287: 13285:

Kamat MA, Blackshaw JA, Young R, Surendran P, Burgess S, Danesh J, et al. (November 2019).

12408:

Müller S, Sindikubwabo F, Cañeque T, Lafon A, Versini A, Lombard B, et al. (October 2020).

3104: 1924:

Somatic epigenetic inheritance, particularly through DNA and histone covalent modifications and

1248: 15353: 14648: 14547: 14532: 14501: 14402: 14180: 14105: 13997: 13507: 11522:

Ballestar E (August 2010). "Epigenetics lessons from twins: prospects for autoimmune disease".

11310:

Oliveira PH, Ribis JW, Garrett EM, Trzilova D, Kim A, Sekulovic O, et al. (January 2020).

10823:"Relics of repeat-induced point mutation direct heterochromatin formation in Neurospora crassa" 10787: 10753: 10627:

van der Graaf A, Wardenaar R, Neumann DA, Taudt A, Shaw RG, Jansen RC, et al. (May 2015).

9857:

Chapter: "Nervous System Development" in "Epigenetics," by Benedikt Hallgrimsson and Brian Hall

8850:"EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity" 8626:"Profiling DNA break sites and transcriptional changes in response to contextual fear learning" 4450:

Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, et al. (June 1999).

2734: 2638: 2133: 1567: 1289: 1277: 1260:. In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides ( 778: 745:

frequently occurs in repeated sequences, and helps to suppress the expression and mobility of '

570:

activity to methylate histone 3 at lysine 9. On the other hand, DNA maintenance methylation by

72:

implies features that are "on top of" or "in addition to" the traditional (DNA sequence based)

9711:"A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility" 9280:

Zhang W, Qu J, Liu GH, Belmonte JC (March 2020). "The ageing epigenome and its rejuvenation".

6822:

Olaharski AJ, Rine J, Marshall BL, Babiarz J, Zhang L, Verdin E, et al. (December 2005).

6217:

Ferguson-Smith AC (July 2011). "Genomic imprinting: the emergence of an epigenetic paradigm".

15438: 15413: 15393: 15030: 15025: 14967: 14881: 14759: 14653: 14580: 14479: 14417: 14412: 14343: 14278: 14095: 14080: 13960: 13842: 13676: 13641: 12465:

Solier S, Müller S, Cañeque T, Versini A, Mansart A, Sindikubwabo F, et al. (May 2023).

5821:

Shorter J, Lindquist S (June 2005). "Prions as adaptive conduits of memory and inheritance".

5358: 4627:

Li E, Beard C, Jaenisch R (November 1993). "Role for DNA methylation in genomic imprinting".

1834: 1711: 1694: 1663:

and maintenance are due to epigenetic alterations that cause the required dynamic changes in

1428: 1398: 1080: 822: 811: 763: 746: 588: 567: 310:. Waddington held that cell fates were established during development in a process he called 288: 11782: 11253:

Manso AS, Chai MH, Atack JM, Furi L, De Ste Croix M, Haigh R, et al. (September 2014).

11096:

Fang G, Munera D, Friedman DI, Mandlik A, Chao MC, Banerjee O, et al. (December 2012).

10821:

Lewis ZA, Honda S, Khlafallah TK, Jeffress JK, Freitag M, Mohn F, et al. (March 2009).

9963:"Transposable elements: targets for early nutritional effects on epigenetic gene regulation" 8107:"Transcriptomic and Epigenomic Dynamics of Honey Bees in Response to Lethal Viral Infection" 7908:

Verma M, Rogers S, Divi RL, Schully SD, Nelson S, Joseph Su L, et al. (February 2014).

5509:"sRNATarBase 2.0 A comprehensive database of bacterial SRNA targets verified by experiments" 3311:

La tentative de Nikolai Koltzoff (Koltsov) de lier génétique, embryologie et chimie physique

2585:

authors making unfounded suggestions that a person's genes and health can be manipulated by

1941:, some stem cells continue producing newly differentiated cells throughout life, such as in 1673: 15765: 15658: 15468: 15418: 15130: 14987: 14836: 14668: 14511: 14506: 14388: 14383: 14370: 14202: 14100: 14018: 13741: 13559: 13013: 12756: 12684:

Hawe JS, Wilson R, Schmid KT, Zhou L, Lakshmanan LN, Lehne BC, et al. (January 2022).

12478: 12421: 11404: 11266: 11047:

Murray IA, Clark TA, Morgan RD, Boitano M, Anton BP, Luong K, et al. (December 2012).

10640: 10434: 10387: 9109: 8861: 8696: 8637: 8577: 8564:

Kitamura T, Ogawa SK, Roy DS, Okuyama T, Morrissey MD, Smith LM, et al. (April 2017).

8393:

Teif VB, Beshnova DA, Vainshtein Y, Marth C, Mallm JP, Höfer T, et al. (August 2014).

8169: 7761: 7594:

Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, et al. (July 2007).

7545: 7431:"Mismatch repair proteins recruit DNA methyltransferase 1 to sites of oxidative DNA damage" 7334: 6735: 6676: 6568: 6411:

Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, et al. (July 2007).

6326: 6273: 5779: 5252: 5197: 4864:"Determination of enriched histone modifications in non-genic portions of the human genome" 4636: 3780: 3723: 3556: 3451: 3402: 3391:"In search of evolutionary developmental mechanisms: the 30-year gap between 1944 and 1974" 3135: 3051: 2664: 2474: 2068: 1991: 1965: 1946: 1492: 1390: 1273: 1165: 855: 846: 515: 511: 303: 261: 111: 98:

The term also refers to the mechanism of changes: functionally relevant alterations to the

13248: 13151:

Guan W, Steffen BT, Lemaitre RN, Wu JH, Tanaka T, Manichaikul A, et al. (June 2014).

12802:

Yengo L, Sidorenko J, Kemper KE, Zheng Z, Wood AR, Weedon MN, et al. (October 2018).

11391:

Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, et al. (July 2005).

11255:"A random six-phase switch regulates pneumococcal virulence via global epigenetic changes" 8444:"Variants of core histones and their roles in cell fate decisions, development and cancer" 7986:. Methods in Molecular Biology. Vol. 463. Clifton, N.J.: Springer. pp. 297–308. 7748:

Russo G, Landi R, Pezone A, Morano A, Zuchegna C, Romano A, et al. (September 2016).

6555:

Gottschalk AJ, Timinszky G, Kong SE, Jin J, Cai Y, Swanson SK, et al. (August 2009).

2013:

is specific to animals, and epigenetic inheritance is more common in plants and microbes.

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regions of genes, the genes are often repressed. When methylated cytosines are present in

164:, which in turn become fully differentiated cells. In other words, as a single fertilized 8: 15775: 15573: 15443: 14999: 14994: 14972: 14918: 14764: 14028: 13821: 13811: 13771: 13671: 13651: 13544: 13539: 13200:

Shin SY, Fauman EB, Petersen AK, Krumsiek J, Santos R, Huang J, et al. (June 2014).

10949:"Entering the era of bacterial epigenomics with single molecule real time DNA sequencing" 7321:

Lan L, Nakajima S, Oohata Y, Takao M, Okano S, Masutani M, et al. (September 2004).

7083:

Hamilton ML, Guo Z, Fuller CD, Van Remmen H, Ward WF, Austad SN, et al. (May 2001).

6514: 2377: 2182: 2176: 2034: 1726: 1722: 1555: 1484: 1415: 1402: 1201: 961: 867: 696: 531: 499: 495: 355:

heritable changes in gene function that cannot be explained by changes in DNA sequence."

103: 13017: 12760: 12499: 12482: 12466: 12425: 11497: 11408: 11270: 10644: 10438: 10391: 9113: 8865: 8768: 8743: 8700: 8641: 8581: 8173: 7765: 7549: 7338: 6739: 6680: 6572: 6330: 6277: 5783: 5589: 5562: 5256: 5201: 4640: 4330: 4305: 3784: 3727: 3560: 3549:

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences

3455: 3406: 3139: 3055: 1318:

activity increases transcription of the gene into messenger RNA. In cells treated with H

15734: 15688: 15668: 15653: 15478: 15473: 14453: 14163: 14046: 13781: 13666: 13661: 13636: 13395: 13383: 13311: 13287:"PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations" 13286: 13226: 13201: 13177: 13152: 13128: 13101: 13082: 13034: 13001: 12977: 12950: 12926: 12901: 12877: 12852: 12828: 12803: 12779: 12744: 12713: 12653: 12610: 12597: 12572: 12548: 12523: 12442: 12409: 12385: 12358: 12334: 12309: 12285: 12258: 12204: 12146: 12137: 12121: 12070: 12045: 12021: 11996: 11972: 11945: 11890: 11659: 11632: 11593: 11566: 11565:

Wallace RG, Twomey LC, Custaud MA, Moyna N, Cummins PM, Mangone M, et al. (2016).

11547: 11478: 11427: 11392: 11336: 11311: 11287: 11254: 11230: 11205: 11186: 11173: 11146: 11122: 11097: 11073: 11048: 11024: 10997: 10973: 10948: 10924: 10899: 10847: 10822: 10779: 10714: 10687: 10663: 10628: 10604: 10579: 10560: 10506: 10481: 10457: 10422: 10360: 10217: 10192: 10168: 10143: 10090: 10036: 10011: 9840: 9748: 9735: 9710: 9660: 9635: 9546: 9492: 9467: 9448: 9400: 9375: 9351: 9324: 9305: 9262: 9219: 9176: 9133: 9082: 9031: 9006: 8982: 8955: 8931: 8906: 8882: 8849: 8827: 8781: 8719: 8684: 8660: 8625: 8598: 8565: 8515: 8490: 8471: 8419: 8394: 8372: 8240: 8192: 8157: 8133: 8106: 8087: 7934: 7909: 7882: 7857: 7833: 7806: 7782: 7749: 7725: 7700: 7676: 7649: 7622: 7595: 7568: 7533: 7509: 7482: 7455: 7430: 7406: 7381: 7298: 7271: 7247: 7222: 7158: 7133: 7057: 7032: 6943: 6935: 6899: 6850: 6823: 6758: 6723: 6699: 6664: 6640: 6615: 6591: 6556: 6490: 6463: 6439: 6412: 6388: 6361: 6299: 6242: 6194: 6169: 6145: 6099: 6045: 6018: 5994: 5967: 5943: 5918: 5894: 5869: 5846: 5803: 5485: 5460: 5414: 5389: 5370: 5322: 5297: 5273: 5240: 5221: 5093: 5019: 4939: 4914: 4890: 4863: 4839: 4814: 4755: 4728: 4704: 4679: 4660: 4609: 4531: 4432: 4386: 4343: 4248: 4223: 4199: 4174: 4150: 4125: 4098: 4074:"Understanding the relationship between DNA methylation and histone lysine methylation" 4073: 4046: 4021: 3990: 3965: 3943: 3900: 3852: 3825: 3801: 3768: 3749: 3692: 3525: 3474: 3439: 3254: 3229: 3159: 3077: 3012: 2985: 2961: 2936: 2912: 2887: 2863: 2838: 2786: 2761: 2684: 2565:

As epigenetics is in the early stages of development as a science and is surrounded by

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The idea that modifications act as docking modules for related factors is borne out by

95:

factors, or be part of normal development. Epigenetic factors can also lead to cancer.

10399: 9987: 9962: 9709:

Sheu SH, Upadhyayula S, Dupuy V, Pang S, Deng F, Wan J, et al. (September 2022).

7481:

Jiang Z, Lai Y, Beaver JM, Tsegay PS, Zhao ML, Horton JK, et al. (January 2020).

7357: 7322: 7031:

Swenberg JA, Lu K, Moeller BC, Gao L, Upton PB, Nakamura J, et al. (March 2011).

6974: 5747: 5722: 5698: 5673: 5390:"N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO" 4915:"Ultrasensitive gene regulation by positive feedback loops in nucleosome modification" 4476: 4451: 3440:"Floral morphogenesis: stochastic explorations of a gene network epigenetic landscape" 2335: 1467:

techniques to further understanding of epigenetic phenomena. These techniques include

1284:

and TET1 oxidizes the 5mC adjacent to the 8-OHdG. This initiates demethylation of 5mC.

407:

refers to global analyses of epigenetic changes across the entire genome. The phrase "

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Schadt EE, Banerjee O, Fang G, Feng Z, Wong WH, Zhang X, et al. (January 2013).

10878: 10852: 10771: 10719: 10668: 10609: 10595: 10552: 10511: 10462: 10403: 10352: 10313: 10285: 10260: 10222: 10173: 10094: 10082: 10041: 10027: 9992: 9978: 9943: 9891: 9805: 9752: 9740: 9665: 9616: 9581: 9550: 9538: 9528: 9497: 9440: 9405: 9356: 9309: 9297: 9266: 9254: 9223: 9211: 9168: 9125: 9074: 9036: 8987: 8936: 8887: 8819: 8773: 8724: 8665: 8603: 8520: 8463: 8424: 8376: 8333: 8308: 8301: 8281: 8271: 8232: 8197: 8138: 8079: 8005: 7995: 7939: 7887: 7838: 7787: 7730: 7681: 7627: 7573: 7514: 7460: 7411: 7362: 7303: 7252: 7203: 7163: 7114: 7109: 7084: 7062: 7013: 6978: 6918: 6891: 6855: 6804: 6763: 6704: 6645: 6596: 6537: 6495: 6444: 6393: 6342: 6291: 6234: 6199: 6150: 6130: 6091: 6050: 5999: 5948: 5899: 5838: 5795: 5752: 5703: 5594: 5561:

Bresnahan ST, Lee E, Clark L, Ma R, Rangel J, Grozinger CM, et al. (June 2023).

5490: 5419: 5362: 5327: 5278: 5264: 5213: 5156: 5085: 5042: 5011: 4944: 4895: 4844: 4795: 4760: 4709: 4652: 4601: 4566: 4523: 4519: 4481: 4424: 4420: 4378: 4335: 4284: 4253: 4204: 4155: 4103: 4051: 3995: 3947: 3935: 3904: 3892: 3857: 3806: 3741: 3684: 3643: 3600: 3574: 3517: 3513: 3479: 3420: 3369: 3259: 3205: 3151: 3069: 3017: 2966: 2952: 2917: 2868: 2791: 2729: 2658: 2462: 2456: 2320: 2286: 2083: 2042: 1753: 1686: 1660: 1464: 1382: 1253: 1169: 1035: 535: 454:

of a cell or individual is affected by which of its genes are transcribed, heritable

364: 343:

More recent usage of the word in biology follows stricter definitions. As defined by

326: 119: 14698: 14247: 13302: 13263: 13168: 12208: 11551: 11482: 10564: 9651: 9483: 9452: 9180: 9137: 8831: 8244: 8156:

Li-Byarlay H, Li Y, Stroud H, Feng S, Newman TC, Kaneda M, et al. (July 2013).

8091: 6303: 6246: 5738: 5374: 5097: 5023: 4436: 4239: 3753: 3696: 3163: 2346: 2227:

Direct comparisons of identical twins constitute an optimal model for interrogating

1414:

transcription start site, and negative numbers indicate nucleotides in the upstream

1362:

incubation appear to promote other epigenetic alterations. Treatment of cells with H

15398: 14724: 14693: 14688: 14643: 14271: 13826: 13801: 13367: 13306: 13298: 13259: 13221: 13213: 13172: 13164: 13123: 13113: 13086: 13066: 13029: 13021: 12972: 12962: 12921: 12913: 12872: 12864: 12823: 12815: 12774: 12764: 12697: 12637: 12592: 12584: 12543: 12535: 12494: 12486: 12437: 12429: 12380: 12370: 12329: 12321: 12280: 12270: 12231: 12186: 12178: 12141: 12133: 12065: 12057: 12016: 12008: 11967: 11957: 11886: 11853: 11814: 11740: 11692: 11654: 11644: 11588: 11578: 11531: 11462: 11422: 11412: 11331: 11323: 11282: 11274: 11225: 11217: 11168: 11158: 11117: 11109: 11068: 11060: 11019: 11009: 10968: 10960: 10919: 10911: 10842: 10834: 10783: 10763: 10709: 10699: 10658: 10648: 10599: 10591: 10542: 10501: 10493: 10482:"The extended evolutionary synthesis and the role of soft inheritance in evolution" 10452: 10442: 10395: 10364: 10344: 10317: 10212: 10204: 10163: 10155: 10072: 10031: 10023: 9982: 9974: 9933: 9883: 9844: 9832: 9797: 9730: 9722: 9655: 9647: 9608: 9573: 9520: 9487: 9479: 9432: 9395: 9387: 9346: 9336: 9289: 9246: 9203: 9160: 9117: 9086: 9066: 9026: 9018: 8977: 8967: 8926: 8918: 8877: 8869: 8811: 8785: 8763: 8755: 8714: 8704: 8655: 8645: 8593: 8585: 8510: 8502: 8475: 8455: 8414: 8406: 8362: 8263: 8224: 8187: 8177: 8128: 8118: 8069: 7987: 7929: 7921: 7910:"Epigenetic research in cancer epidemiology: trends, opportunities, and challenges" 7877: 7869: 7828: 7818: 7777: 7769: 7720: 7712: 7671: 7661: 7617: 7607: 7563: 7553: 7504: 7494: 7450: 7442: 7401: 7393: 7352: 7342: 7293: 7283: 7242: 7234: 7195: 7153: 7145: 7132:

Ming X, Matter B, Song M, Veliath E, Shanley R, Jones R, et al. (March 2014).

7104: 7096: 7052: 7044: 7005: 6970: 6910: 6903: 6883: 6845: 6835: 6794: 6753: 6743: 6694: 6684: 6635: 6627: 6614:

Lin JC, Jeong S, Liang G, Takai D, Fatemi M, Tsai YC, et al. (November 2007).

6586: 6576: 6529: 6485: 6475: 6434: 6424: 6383: 6373: 6334: 6281: 6226: 6189: 6181: 6140: 6122: 6103: 6081: 6040: 6030: 5989: 5979: 5938: 5930: 5889: 5881: 5850: 5830: 5807: 5787: 5742: 5734: 5693: 5685: 5652: 5621: 5584: 5574: 5480: 5472: 5409: 5401: 5354: 5317: 5309: 5268: 5260: 5225: 5205: 5148: 5120: 5075: 5001: 4934: 4926: 4885: 4875: 4834: 4826: 4787: 4750: 4740: 4699: 4691: 4664: 4644: 4613: 4593: 4558: 4535: 4515: 4471: 4463: 4416: 4390: 4370: 4347: 4325: 4317: 4276: 4243: 4235: 4194: 4186: 4145: 4137: 4093: 4085: 4041: 4033: 3985: 3977: 3927: 3884: 3847: 3837: 3796: 3788: 3731: 3674: 3633: 3564: 3529: 3509: 3469: 3459: 3410: 3249: 3241: 3143: 3081: 3059: 3007: 2997: 2956: 2948: 2907: 2899: 2858: 2850: 2781: 2773: 2704: 2431:. This leads to epigenetic effects through inhibition of α-ketoglutarate-dependent 2232: 2146: 2010: 1613: 1327: 1265: 970: 825:

can modulate transcriptional gene expression via epigenetic modulation of targeted

750: 559: 487: 266: 252: 88: 12900:

Zhu Z, Guo Y, Shi H, Liu CL, Panganiban RA, Chung W, et al. (February 2020).

8905:

Manzo M, Wirz J, Ambrosi C, Villaseñor R, Roschitzki B, Baubec T (December 2017).

7925: 7323:"In situ analysis of repair processes for oxidative DNA damage in mammalian cells" 7199: 6616:"Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG island" 5689: 4562: 1042:

and express dormant genetic features normally terminated by stop codon mutations.

395:

The similarity of the word to "genetics" has generated many parallel usages. The "

15683: 15648: 15135: 14861: 14734: 14638: 14448: 14224: 14061: 13907: 13686: 12967: 11918: 11649: 11014: 10704: 8650: 8538: 8353:

Serizay J, Dong Y, Jänes J, Chesney M, Cerrato C, Ahringer J (20 February 2020).

8267: 7991: 7666: 7612: 6840: 6748: 6689: 6480: 6429: 6338: 6121:. Advances in Experimental Medicine and Biology. Vol. 962. pp. 95–102. 5527:"Genomics maps for small non-coding RNA's and their targets in microbial genomes" 5152: 4584:

Robertson KD, Wolffe AP (October 2000). "DNA methylation in health and disease".

4500: 4175:"The role of histone tails in nucleosome stability: An electrostatic perspective" 4089: 3464: 3344: 2719: 2714: 2624: 2574: 2470: 2420: 2396: 2273: 2255: 1902: 1235: 1124: 1120: 1104: 1092: 895: 774: 742: 700: 664: 459: 424: 412: 385: 322: 244: 107: 10159: 9636:"Physical exercise as an epigenetic modulator of brain plasticity and cognition" 9524: 8685:"Real-time visualization of mRNA synthesis during memory formation in live mice" 6126: 5934: 2854: 2117: 2071:

the adaptive phenotypic change. The existence of this possibility increases the

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