966:"Epigenetic age" refers to the connection between chronological age and levels of DNA methylation in the genome. Coupling the levels of DNA methylation, in specific sets of CpGs called "clock CpGs", with algorithms that regress the typical levels of collective genome-wide methylation at a given chronological age, allow for epigenetic age prediction. During youth (0–20 years old), changes in DNA methylation occur at a faster rate as development and growth progresses, and the changes begin to slow down at older ages. Multiple epigenetic age estimators exist. Horvath's clock measures a multi-tissue set of 353 CpGs, half of which positively correlate with age, and the other half negatively, to estimate the epigenetic age. Hannum's clock utilizes adult blood samples to calculate age based on an orthogonal basis of 71 CpGs. Levine's clock, known as DNAm PhenoAge, depends on 513 CpGs and surpasses the other age estimators in predicting mortality and lifespan, yet displays bias with non-blood tissues. There are reports of age estimators with the methylation state of only one CpG in the gene ELOVL2. Estimation of age allows for prediction lifespan through expectations of age related conditions that individuals may be subject to based on their 5mC methylation markers.
830:
874:
324:
197:
470:
949:
the abnormal levels of 5mC in cancer. Repeat sequences in the genome, including satellite DNA, Alu, and long interspersed elements (LINE), are often seen hypomethylated in cancer, resulting in expression of these normally silenced genes, and levels are often significant markers of tumor progression. It has been hypothesized that there a connection between the hypermethylation and hypomethylation; over activity of DNA methyltransferases that produce the abnormal
29:
857:(DNMTs). There are 5 DNMTs in humans: DNMT1, DNMT2, DNMT3A, DNMT3B, and DNMT3L, and in algae and fungi 3 more are present (DNMT4, DNMT5, and DNMT6). DNMT1 contains the replication foci targeting sequence (RFTS) and the CXXC domain which catalyze the addition of 5mC marks. RFTS directs DNMT1 to loci of DNA replication to assist in the maintenance of 5mC on daughter strands during DNA replication, whereas CXXC contains a
574:
907:(TDG), followed by base excision repair (BER) to restore the cytosine. TDG knockout produced a 2-fold increase of 5fC without any statistically significant change to levels of 5hmC, indicating 5mC must be iteratively oxidized at least twice before its full demethylation. The oxidation occurs through the
948:
methylated resulting in aberrant inactivation of genes normally associated with growth inhibition of tumors (an example of hypermethylation). Comparing tumor and normal tissue, the former had elevated levels of the methyltransferases DNMT1, DNMT3A, and mostly DNMT3B, all of which are associated with
869:
methylation, and DNMT1 maintains the 5mC mark after replication. DNMTs can interact with each other to increase methylating capability. For example, 2 DNMT3L can form a complex with 2 DNMT3A to improve interactions with the DNA, facilitating the methylation. Changes in the expression of DNMT results
894:
After a cytosine is methylated to 5mC, it can be reversed back to its initial state via multiple mechanisms. Passive DNA demethylation by dilution eliminates the mark gradually through replication by a lack of maintenance by DNMT. In active DNA demethylation, a series of oxidations converts it to
953:
5mC methylation may be compensated by the removal of methylation, a type of epigenetic repair. However, the removal of methylation is inefficient resulting in an overshoot of genome-wide hypomethylation. The contrary may also be possible; over expression of hypomethylation may be silenced by
915:) which can convert 5mC, 5hmC, and 5fC to their oxidized forms. However, the enzyme has the greatest preference for 5mC and the initial reaction rate for 5hmC and 5fC conversions with TET2 are 4.9-7.6 fold slower. TET requires Fe(II) as cofactor, and oxygen and
954:
genome-wide hypermethylation. Cancer hallmark capabilities are likely acquired through epigenetic changes that alter the 5mC in both the cancer cells and in surrounding tumor-associated stroma within the tumor microenvironment. The anticancer drug
885:
then donates a methyl group to carbon 5. A base in the DNMT enzyme deprotonates the residual hydrogen on carbon 5 restoring the double bond between carbon 5 and 6 in the ring, producing the 5-methylcytosine base pair.
478:
450:
2466:
Garagnani P, Bacalini MG, Pirazzini C, Gori D, Giuliani C, Mari D, Blasio AM, Gentilini D, Vitale G, Collino S, Rezzi S (2012). "Methylation of ELOVL2 gene as a new epigenetic marker of age".
881:
The mechanism of the addition is as follows: first a cysteine residue on the DNMT's PCQ motif creates a nucleophillic attack at carbon 6 on the cytosine nucleotide that is to be methylated.
536:
865:
addition of methylation to the DNA. DNMT1 was found to be the predominant DNA methyltransferase in all human tissue. Primarily, DNMT3A and DNMT3B are responsible for
800:
family of cytosine deaminases could have beneficial implications on various cellular processes as well as on organismal evolution. The implications of deamination on
2313:
750:
In bacteria, 5-methylcytosine can be found at a variety of sites, and is often used as a marker to protect DNA from being cut by native methylation-sensitive
587:
626:
2552:
373:
870:
in aberrant methylation. Overexpression produces increased methylation, whereas disruption of the enzyme decreased levels of methylation.
1254:
1647:"The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors"
841:
treatment, which deaminates cytosine residues. This property is often exploited to analyze DNA cytosine methylation patterns with
705:. This report was severely criticized because their identification was based solely on the optical properties of the crystalline
2409:
Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S, Hou L, Baccarelli AA, Stewart JD, Li Y, Whitsel EA (2018-04-17).
582:
97:
1453:
Chahwan R, Wontakal SN, Roa S (2010). "Crosstalk between genetic and epigenetic information through cytosine deamination".
2352:
Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, Fan JB, Gao Y, Deconde R (2013-01-24).
1050:
2540:
776:. In mammalian cells, clusters of CpG at the 5' ends of genes are termed CpG islands. 1% of all mammalian DNA is 5mC.
338:
625:
and takes several other biological roles. When cytosine is methylated, the DNA maintains the same sequence, but the
2548:
709:, and other scientists failed to reproduce the same result. But its existence was ultimately proven in 1948, when
594:
1066:
Johnson TB, Coghill RD (1925). "The discovery of 5-methyl-cytosine in tuberculinic acid, the nucleic acid of the
248:
104:
2194:
Horvath S, Raj K (June 2018). "DNA methylation-based biomarkers and the epigenetic clock theory of ageing".
1589:
Lyko F (February 2018). "The DNA methyltransferase family: a versatile toolkit for epigenetic regulation".
510:
281:
192:
302:
1948:"Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases"
1767:
Song CX, Szulwach KE, Dai Q, Fu Y, Mao SQ, Lin L, Street C, Li Y, Poidevin M, Wu H, Gao J (2013-04-25).
528:
927:(2HG) which competes with α-KG, reducing TET activity, and in turn reducing conversion of 5mC to 5hmC.
677:
469:
2583:
988:
Wu X, Zhang Y (2017-05-30). "TET-mediated active DNA demethylation: mechanism, function and beyond".
697:
and
Coghill successfully detected a minor amount of a methylated cytosine derivative as a product of
544:
204:
524:
319:
920:
728:, by which he detected a unique methylated cytosine, quite distinct from conventional cytosine and
710:
622:
242:
1946:
Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu Lx (2011-01-18).
904:
896:
801:
1192:
Squires JE, Patel HR, Nousch M, Sibbritt T, Humphreys DT, Parker BJ, Suter CM, Preiss T (2012).
772:
methylate only a small percentage of these sites, but 70-80% of CpG cytosines are methylated in
122:
1396:"Mutagenic consequences of cytosine alterations site-specifically embedded in the human genome"
788:, which is recognized and removed by DNA repair enzymes, deamination of 5-methylcytosine forms
1112:"Microbial nucleic acids: the desoxypentose nucleic acids of avian tubercle bacilli and yeast"
2155:"Formation of Cisplatin Adducts with the Epigenetically-relevant Nucleobase 5-Methylcytosine"
1645:
Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA (1999-06-01).
1153:"The quantitative separation of purines, pyrimidines and nucleosides by paper chromatography"
882:
854:
793:
694:
651:
at the six o'clock position. This methyl group distinguishes 5-methylcytosine from cytosine.
647:
is attached to the 5th atom in the 6-atom ring, counting counterclockwise from the NH-bonded
492:
462:
548:
2573:
2568:
1891:"TET Family Proteins: Oxidation Activity, Interacting Molecules, and Functions in Diseases"
1837:
1715:
1407:
1352:
1293:
1098:
Nucleic Acids Are Not Boring Long
Polymers of Only Four Types of Nucleotides: A Guided Tour
944:, and under-methylated, termed hypomethylation. CpG islands overlapping gene promoters are
842:
725:
290:
174:
41:
919:(α-KG) as substrates, and the latter substrate is generated from isocitrate by the enzyme
829:
8:
2578:
1538:
751:
73:
63:
2066:
1841:
1719:
1411:
1356:
1297:
323:
196:
154:
2509:
2443:
2410:
2386:
2353:
2281:
2246:
2227:
2042:
2009:
1980:
1947:
1923:
1890:
1866:
1825:
1801:
1768:
1744:
1703:
1622:
1430:
1395:
1325:
1266:
1218:
1193:
1021:
924:
134:
1826:"Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine"
1679:
1646:
1514:
1489:
1241:
Colot V, Rossignol JL (1999). "Eukaryotic DNA methylation as an evolutionary device".
1169:
1152:
1128:
1111:
916:
2536:
2501:
2493:
2448:
2430:
2391:
2373:
2305:
2286:
2268:
2219:
2211:
2176:
2135:
2127:
2086:
2078:
2047:
2029:
1985:
1967:
1928:
1910:
1871:
1853:
1806:
1788:
1749:
1731:
1684:
1666:
1614:
1606:
1568:
1560:
1519:
1470:
1435:
1376:
1368:
1317:
1309:
1258:
1223:
1174:
1133:
1097:
1046:
1013:
1005:
672:
1626:
1270:
2513:
2483:
2475:
2438:
2422:
2381:
2365:
2334:
2326:
2297:
2276:
2258:
2231:
2203:
2166:
2117:
2037:
2021:
1975:
1959:
1918:
1902:
1861:
1845:
1796:
1780:
1769:"Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming"
1739:
1723:
1674:
1658:
1598:
1550:
1509:
1501:
1462:
1425:
1415:
1360:
1329:
1301:
1250:
1213:
1205:
1164:
1123:
1079:
1025:
997:
941:
903:(5fC), and 5-carboxylcytosine (5caC), and the latter two are eventually excised by
900:
796:. In addition, active enzymatic deamination of cytosine or 5-methylcytosine by the
732:. After seven decades, it turned out that it is also a common feature in different
637:
401:
1824:
Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y (2011-09-02).
1704:"Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation"
270:
2369:
2354:"Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates"
1040:
792:. This conversion of a DNA base from cytosine (C) to thymine (T) can result in a
681:. The nucleic acid was found to be unusual, in that it contained in addition to
2263:
2122:
2105:
1784:
565:
516:
2301:
2207:
1963:
1539:"Evolutionary Diversification of DNA Methyltransferases in Eukaryotic Genomes"
1466:
1420:
1194:"Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA"
2562:
2497:
2434:
2377:
2272:
2215:
2180:
2131:
2082:
2033:
1971:
1914:
1857:
1792:
1735:
1670:
1662:
1610:
1564:
1505:
1372:
1313:
1009:
718:
702:
185:
1849:
1555:
1364:
1284:
Bird AP (May 1986). "CpG-rich islands and the function of DNA methylation".
2505:
2452:
2395:
2309:
2290:
2223:
2171:
2154:
2139:
2051:
1989:
1932:
1875:
1810:
1753:
1688:
1618:
1572:
1474:
1439:
1262:
1227:
1178:
1137:
1017:
823:
668:
664:
644:
2426:
2090:
1523:
1380:
1321:
873:
1255:
10.1002/(SICI)1521-1878(199905)21:5<402::AID-BIES7>3.0.CO;2-B
1209:
912:
908:
858:
781:
630:
610:
540:
2488:
2323:
has been checked and does not affect the cited material, please replace
1727:
1602:
1083:
1001:
532:
2479:
1343:
Ehrlich M, Wang RY (1981-06-19). "5-Methylcytosine in eukaryotic DNA".
773:
698:
634:
432:
205:
165:
2025:
1906:
552:
1305:
955:
838:
769:
564:
Except where otherwise noted, data are given for materials in their
1702:
Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X (September 2007).
765:
758:
690:
648:
618:
231:
28:
848:
746:
The function of this chemical varies significantly among species:
556:
103:
96:
2320:
1446:
819:
818:
group can be removed (deamination) from 5-methylcytosine to form
789:
706:
686:
682:
520:
498:
257:
797:
785:
764:
In fungi and animals, 5-methylcytosine predominantly occurs at
729:
721:
2465:
2411:"An epigenetic biomarker of aging for lifespan and healthspan"
1644:
826:; cytosine deaminates to uracil (U) under similar conditions.
2153:
Menke A, Dubini RC, Mayer P, Rovó P, Daumann L (2020-10-23).
660:
145:
86:
307:
1394:
Sassa A, Kanemaru Y, Kamoshita N, Honma M, Yasui M (2016).
1393:
502:
222:
2535:. San Francisco: W.H. Freeman. Chapter 15: Gene Mutation.
1191:
629:
can be altered (the study of this is part of the field of
347:
InChI=1S/C5H7N3O/c1-3-2-7-5(9)8-4(3)6/h2H,1H3,(H3,6,7,8,9)
940:
In cancer, DNA can become both overly methylated, termed
733:
714:
614:
357:
InChI=1/C5H7N3O/c1-3-2-7-5(9)8-4(3)6/h2H,1H3,(H3,6,7,8,9)
2530:
1701:
1487:
1109:
2351:
2247:"DNA methylation age of human tissues and cell types"
2152:
736:molecules, although the precise role is uncertain.
1490:"High sensitivity mapping of methylated cytosines"
1452:
761:, CpHpG and CpHpH sequences (where H = A, C or T).
2408:
1766:
1488:Clark SJ, Harrison J, Paul CL, Frommer M (1994).
121:
2560:
1045:. Williams & Wilkins Company/. p. 167.
911:(Ten-eleven translocation) family dioxygenases (
837:5-methylcytosine is resistant to deamination by
269:
2103:
849:Addition and regulation with DNMTs (Eukaryotes)
72:
1240:
1065:
804:, on the other hand, remains less understood.
16:Chemical compound which is a modified DNA base
2553:National Center for Biotechnology Information
1945:
1823:
1342:
633:). 5-Methylcytosine is incorporated in the
2193:
2106:"Hallmarks of Cancer: The Next Generation"
1110:Vischer E, Zamenhof S, Chargaff E (1949).
961:
833:Deamination of 5-methylcytosine to thymine
322:
195:
173:
2487:
2442:
2385:
2280:
2262:
2170:
2121:
2041:
1979:
1922:
1865:
1800:
1743:
1678:
1554:
1513:
1429:
1419:
1217:
1168:
1150:
1127:
289:
1888:
1536:
1038:
872:
853:5mC marks are placed on genomic DNA via
828:
2244:
2159:European Journal of Inorganic Chemistry
2007:
987:
318:
247:
2561:
2337:|...|checked=yes}}
2003:
2001:
1999:
757:In plants, 5-methylcytosine occurs at
659:While trying to isolate the bacterial
186:
2104:Hanahan D, Weinberg RA (2011-03-04).
2064:
2010:"DNA hypomethylation in cancer cells"
1640:
1638:
1636:
1584:
1582:
958:has been reported to react with 5mC.
350:Key: LRSASMSXMSNRBT-UHFFFAOYSA-N
153:
1588:
1283:
983:
981:
979:
877:Addition of methyl group to cytosine
693:, a methylated nucleotide. In 1925,
2533:An Introduction to genetic analysis
2067:"DNA Methylation Errors and Cancer"
1996:
360:Key: LRSASMSXMSNRBT-UHFFFAOYAO
260:
230:
13:
1889:Lu X, Zhao BS, He C (2015-02-12).
1633:
1579:
923:(IDH). Cancer however can produce
14:
2595:
2531:Griffiths, Anthony J. F. (1999).
976:
930:
889:
572:
468:
419:
413:
27:
2459:
2402:
2345:
2238:
2187:
2146:
2097:
2058:
1939:
1882:
1817:
1760:
1695:
1543:Molecular Biology and Evolution
1530:
1481:
1387:
1336:
713:separated the nucleic acids of
667:, W.G. Ruppel isolated a novel
568:(at 25 °C , 100 kPa).
1537:Ponger L, Li WH (2005-04-01).
1277:
1234:
1185:
1144:
1103:
1090:
1059:
1032:
627:expression of methylated genes
425:
407:
1:
2524:
1170:10.1016/S0021-9258(18)57261-6
1129:10.1016/S0021-9258(18)57100-3
969:
822:with use of reagents such as
46:4-Amino-5-methylpyrimidin-2(1
2370:10.1016/j.molcel.2012.10.016
935:
654:
7:
807:
10:
2600:
2264:10.1186/gb-2013-14-10-r115
2123:10.1016/j.cell.2011.02.013
1785:10.1016/j.cell.2013.04.001
739:
701:of tuberculinic acid with
2302:10.1186/s13059-015-0649-6
2208:10.1038/s41576-018-0004-3
1964:10.1016/j.ccr.2010.12.014
1467:10.1016/j.tig.2010.07.005
1421:10.1186/s41021-016-0045-9
562:
449:
444:
394:
369:
334:
56:
40:
35:
26:
2245:Horvath S (2013-12-10).
2008:Ehrlich M (2009-12-01).
921:isocitrate dehydrogenase
621:(C) that regulates gene
511:Precautionary statements
2196:Nature Reviews Genetics
2065:Jones PA (1996-06-01).
1850:10.1126/science.1210597
1591:Nature Reviews Genetics
1365:10.1126/science.6262918
1042:Physiological Chemistry
990:Nature Reviews Genetics
962:As a biomarker of aging
905:thymine DNA glycosylase
897:5-hydroxymethylcytosine
802:5-hydroxymethylcytosine
643:In 5-methylcytosine, a
2172:10.1002/ejic.202000898
1663:10.1093/nar/27.11.2291
1651:Nucleic Acids Research
1506:10.1093/nar/22.15.2990
878:
855:DNA methyltransferases
834:
2551:at the United States
2427:10.18632/aging.101414
2329:|...}}
1556:10.1093/molbev/msi098
1400:Genes and Environment
1151:Hotchkiss RD (1948).
876:
832:
381:O=C1/N=C\C(=C(\N)N1)C
1100:. Landes Bioscience.
1039:Matthews AP (2012).
883:S-Adenosylmethionine
843:bisulfite sequencing
768:dinucleotides. Most
726:paper chromatography
42:Preferred IUPAC name
1842:2011Sci...333.1300I
1836:(6047): 1300–1303.
1728:10.1038/nature06146
1720:2007Natur.449..248J
1603:10.1038/nrg.2017.80
1412:2016GeneE..38...17S
1357:1981Sci...212.1350E
1351:(4501): 1350–1357.
1298:1986Natur.321..209B
1096:Grosjean H (2009).
1084:10.1021/ja01688a030
1002:10.1038/nrg.2017.33
794:transition mutation
752:restriction enzymes
440: g·mol
135:Beilstein Reference
23:
2480:10.1111/acel.12005
1455:Trends in Genetics
1210:10.1093/nar/gks144
925:2-hydroxyglutarate
879:
835:
784:of cytosine forms
780:While spontaneous
595:Infobox references
21:
2415:Aging (Albany NY)
2077:(11): 2463–2467.
2026:10.2217/epi.09.33
1907:10.1021/cr500470n
1714:(7159): 248–251.
1657:(11): 2291–2298.
1500:(15): 2990–2997.
1494:Nucleic Acids Res
1292:(6067): 209–213.
1204:(11): 5023–5033.
1198:Nucleic Acids Res
1078:(11): 2838–2844.
1068:Tubercle bacillus
678:Tubercle bacillus
673:tuberculinic acid
603:Chemical compound
601:
600:
493:Hazard statements
303:CompTox Dashboard
105:Interactive image
98:Interactive image
22:5-Methylcytosine
2591:
2584:Methyl compounds
2549:available online
2546:
2518:
2517:
2491:
2474:(6): 1132–1134.
2463:
2457:
2456:
2446:
2406:
2400:
2399:
2389:
2349:
2343:
2342:
2340:
2338:
2330:
2315:Retraction Watch
2294:
2284:
2266:
2242:
2236:
2235:
2191:
2185:
2184:
2174:
2150:
2144:
2143:
2125:
2101:
2095:
2094:
2062:
2056:
2055:
2045:
2005:
1994:
1993:
1983:
1943:
1937:
1936:
1926:
1901:(6): 2225–2239.
1895:Chemical Reviews
1886:
1880:
1879:
1869:
1821:
1815:
1814:
1804:
1764:
1758:
1757:
1747:
1699:
1693:
1692:
1682:
1642:
1631:
1630:
1586:
1577:
1576:
1558:
1549:(4): 1119–1128.
1534:
1528:
1527:
1517:
1485:
1479:
1478:
1450:
1444:
1443:
1433:
1423:
1391:
1385:
1384:
1340:
1334:
1333:
1306:10.1038/321209a0
1281:
1275:
1274:
1238:
1232:
1231:
1221:
1189:
1183:
1182:
1172:
1148:
1142:
1141:
1131:
1107:
1101:
1094:
1088:
1087:
1063:
1057:
1056:
1036:
1030:
1029:
985:
942:hypermethylation
901:5-formylcytosine
663:responsible for
638:5-methylcytidine
607:5-Methylcytosine
585:
579:
576:
575:
558:
554:
550:
546:
542:
538:
534:
530:
526:
522:
518:
504:
500:
472:
439:
427:
421:
415:
409:
402:Chemical formula
327:
326:
311:
309:
293:
273:
262:
251:
249:5-Methylcytosine
234:
207:
199:
188:
177:
157:
125:
107:
100:
76:
31:
24:
20:
2599:
2598:
2594:
2593:
2592:
2590:
2589:
2588:
2559:
2558:
2543:
2527:
2522:
2521:
2464:
2460:
2407:
2403:
2350:
2346:
2332:
2324:
2318:
2296:(Erratum:
2295:
2243:
2239:
2192:
2188:
2151:
2147:
2102:
2098:
2071:Cancer Research
2063:
2059:
2006:
1997:
1944:
1940:
1887:
1883:
1822:
1818:
1765:
1761:
1700:
1696:
1643:
1634:
1587:
1580:
1535:
1531:
1486:
1482:
1461:(10): 443–448.
1451:
1447:
1392:
1388:
1341:
1337:
1282:
1278:
1239:
1235:
1190:
1186:
1149:
1145:
1108:
1104:
1095:
1091:
1064:
1060:
1053:
1037:
1033:
986:
977:
972:
964:
938:
933:
917:α-ketoglutarate
892:
851:
817:
812:
744:
657:
604:
597:
592:
591:
590: ?)
581:
577:
573:
569:
513:
495:
481:
465:
437:
424:
418:
412:
404:
390:
387:
382:
377:
376:
365:
362:
361:
358:
352:
351:
348:
342:
341:
330:
312:
305:
296:
276:
263:
237:
217:
180:
160:
137:
128:
110:
90:
79:
66:
52:
51:
17:
12:
11:
5:
2597:
2587:
2586:
2581:
2576:
2571:
2557:
2556:
2541:
2526:
2523:
2520:
2519:
2458:
2421:(4): 573–591.
2401:
2364:(2): 359–367.
2358:Molecular Cell
2344:
2251:Genome Biology
2237:
2202:(6): 371–384.
2186:
2145:
2116:(5): 646–674.
2096:
2057:
2020:(2): 239–259.
1995:
1938:
1881:
1816:
1779:(3): 678–691.
1759:
1694:
1632:
1578:
1529:
1480:
1445:
1386:
1335:
1276:
1249:(5): 402–411.
1233:
1184:
1163:(1): 315–332.
1143:
1122:(1): 429–438.
1102:
1089:
1058:
1052:978-1130145373
1051:
1031:
996:(9): 517–534.
974:
973:
971:
968:
963:
960:
937:
934:
932:
931:Role in humans
929:
891:
888:
850:
847:
815:
811:
806:
778:
777:
762:
755:
743:
738:
656:
653:
602:
599:
598:
593:
571:
570:
566:standard state
563:
560:
559:
537:P305+P351+P338
514:
509:
506:
505:
496:
491:
488:
487:
482:
477:
474:
473:
466:
461:
458:
457:
447:
446:
442:
441:
435:
429:
428:
422:
416:
410:
405:
400:
397:
396:
392:
391:
389:
388:
385:
383:
380:
372:
371:
370:
367:
366:
364:
363:
359:
356:
355:
353:
349:
346:
345:
337:
336:
335:
332:
331:
329:
328:
320:DTXSID50203948
315:
313:
301:
298:
297:
295:
294:
286:
284:
278:
277:
275:
274:
266:
264:
256:
253:
252:
245:
239:
238:
236:
235:
227:
225:
219:
218:
216:
215:
211:
209:
201:
200:
190:
182:
181:
179:
178:
170:
168:
162:
161:
159:
158:
150:
148:
142:
141:
138:
133:
130:
129:
127:
126:
118:
116:
112:
111:
109:
108:
101:
93:
91:
84:
81:
80:
78:
77:
69:
67:
62:
59:
58:
54:
53:
45:
44:
38:
37:
33:
32:
15:
9:
6:
4:
3:
2:
2596:
2585:
2582:
2580:
2577:
2575:
2572:
2570:
2567:
2566:
2564:
2554:
2550:
2544:
2542:0-7167-3520-2
2538:
2534:
2529:
2528:
2515:
2511:
2507:
2503:
2499:
2495:
2490:
2485:
2481:
2477:
2473:
2469:
2462:
2454:
2450:
2445:
2440:
2436:
2432:
2428:
2424:
2420:
2416:
2412:
2405:
2397:
2393:
2388:
2383:
2379:
2375:
2371:
2367:
2363:
2359:
2355:
2348:
2336:
2328:
2322:
2317:
2316:
2311:
2307:
2303:
2299:
2292:
2288:
2283:
2278:
2274:
2270:
2265:
2260:
2256:
2252:
2248:
2241:
2233:
2229:
2225:
2221:
2217:
2213:
2209:
2205:
2201:
2197:
2190:
2182:
2178:
2173:
2168:
2164:
2160:
2156:
2149:
2141:
2137:
2133:
2129:
2124:
2119:
2115:
2111:
2107:
2100:
2092:
2088:
2084:
2080:
2076:
2072:
2068:
2061:
2053:
2049:
2044:
2039:
2035:
2031:
2027:
2023:
2019:
2015:
2011:
2004:
2002:
2000:
1991:
1987:
1982:
1977:
1973:
1969:
1965:
1961:
1957:
1953:
1949:
1942:
1934:
1930:
1925:
1920:
1916:
1912:
1908:
1904:
1900:
1896:
1892:
1885:
1877:
1873:
1868:
1863:
1859:
1855:
1851:
1847:
1843:
1839:
1835:
1831:
1827:
1820:
1812:
1808:
1803:
1798:
1794:
1790:
1786:
1782:
1778:
1774:
1770:
1763:
1755:
1751:
1746:
1741:
1737:
1733:
1729:
1725:
1721:
1717:
1713:
1709:
1705:
1698:
1690:
1686:
1681:
1676:
1672:
1668:
1664:
1660:
1656:
1652:
1648:
1641:
1639:
1637:
1628:
1624:
1620:
1616:
1612:
1608:
1604:
1600:
1596:
1592:
1585:
1583:
1574:
1570:
1566:
1562:
1557:
1552:
1548:
1544:
1540:
1533:
1525:
1521:
1516:
1511:
1507:
1503:
1499:
1495:
1491:
1484:
1476:
1472:
1468:
1464:
1460:
1456:
1449:
1441:
1437:
1432:
1427:
1422:
1417:
1413:
1409:
1405:
1401:
1397:
1390:
1382:
1378:
1374:
1370:
1366:
1362:
1358:
1354:
1350:
1346:
1339:
1331:
1327:
1323:
1319:
1315:
1311:
1307:
1303:
1299:
1295:
1291:
1287:
1280:
1272:
1268:
1264:
1260:
1256:
1252:
1248:
1244:
1237:
1229:
1225:
1220:
1215:
1211:
1207:
1203:
1199:
1195:
1188:
1180:
1176:
1171:
1166:
1162:
1158:
1154:
1147:
1139:
1135:
1130:
1125:
1121:
1117:
1113:
1106:
1099:
1093:
1085:
1081:
1077:
1073:
1072:J Am Chem Soc
1069:
1062:
1054:
1048:
1044:
1043:
1035:
1027:
1023:
1019:
1015:
1011:
1007:
1003:
999:
995:
991:
984:
982:
980:
975:
967:
959:
957:
952:
947:
943:
928:
926:
922:
918:
914:
910:
906:
902:
898:
890:Demethylation
887:
884:
875:
871:
868:
864:
860:
856:
846:
844:
840:
831:
827:
825:
821:
810:
805:
803:
799:
795:
791:
787:
783:
775:
771:
767:
763:
760:
756:
753:
749:
748:
747:
742:
737:
735:
731:
727:
723:
720:
716:
712:
708:
704:
703:sulfuric acid
700:
696:
692:
688:
684:
680:
679:
675:in 1898 from
674:
670:
666:
662:
652:
650:
646:
641:
639:
636:
632:
628:
624:
623:transcription
620:
616:
612:
608:
596:
589:
584:
567:
561:
515:
512:
508:
507:
497:
494:
490:
489:
486:
483:
480:
476:
475:
471:
467:
464:
460:
459:
455:
453:
448:
443:
436:
434:
431:
430:
406:
403:
399:
398:
393:
386:Cc1cnc(=O)c1N
384:
379:
378:
375:
368:
354:
344:
343:
340:
333:
325:
321:
317:
316:
314:
304:
300:
299:
292:
288:
287:
285:
283:
280:
279:
272:
268:
267:
265:
259:
255:
254:
250:
246:
244:
241:
240:
233:
229:
228:
226:
224:
221:
220:
213:
212:
210:
208:
203:
202:
198:
194:
191:
189:
187:ECHA InfoCard
184:
183:
176:
172:
171:
169:
167:
164:
163:
156:
152:
151:
149:
147:
144:
143:
139:
136:
132:
131:
124:
120:
119:
117:
114:
113:
106:
102:
99:
95:
94:
92:
88:
83:
82:
75:
71:
70:
68:
65:
61:
60:
55:
49:
43:
39:
34:
30:
25:
19:
2532:
2489:11585/128353
2471:
2467:
2461:
2418:
2414:
2404:
2361:
2357:
2347:
2333:{{
2325:{{
2314:
2312:,
2257:(10): 3156.
2254:
2250:
2240:
2199:
2195:
2189:
2162:
2158:
2148:
2113:
2109:
2099:
2074:
2070:
2060:
2017:
2013:
1958:(1): 17–30.
1955:
1951:
1941:
1898:
1894:
1884:
1833:
1829:
1819:
1776:
1772:
1762:
1711:
1707:
1697:
1654:
1650:
1597:(2): 81–92.
1594:
1590:
1546:
1542:
1532:
1497:
1493:
1483:
1458:
1454:
1448:
1403:
1399:
1389:
1348:
1344:
1338:
1289:
1285:
1279:
1246:
1242:
1236:
1201:
1197:
1187:
1160:
1156:
1146:
1119:
1115:
1105:
1092:
1075:
1071:
1067:
1061:
1041:
1034:
993:
989:
965:
950:
945:
939:
893:
880:
866:
862:
852:
836:
824:nitrous acid
813:
808:
779:
745:
740:
676:
669:nucleic acid
665:tuberculosis
658:
645:methyl group
642:
613:form of the
606:
605:
484:
451:
57:Identifiers
47:
18:
2574:Pyrimidones
2569:Nucleobases
2014:Epigenomics
1952:Cancer Cell
1157:J Biol Chem
1116:J Biol Chem
913:TET enzymes
861:domain for
859:zinc finger
782:deamination
774:vertebrates
631:epigenetics
479:Signal word
395:Properties
193:100.008.236
155:CHEBI:27551
2579:Biomarkers
2563:Categories
2525:Literature
2468:Aging Cell
970:References
770:eukaryotes
699:hydrolysis
635:nucleoside
611:methylated
463:Pictograms
433:Molar mass
291:6R795CQT4H
166:ChemSpider
85:3D model (
64:CAS Number
2498:1474-9726
2435:1945-4589
2378:1097-2765
2319:. If the
2273:1474-760X
2216:1471-0064
2181:1434-1948
2165:: 30–36.
2132:0092-8674
2083:0008-5472
2034:1750-1911
1972:1535-6108
1915:0009-2665
1858:0036-8075
1793:1097-4172
1736:1476-4687
1671:0305-1048
1611:1471-0064
1565:0737-4038
1406:(1): 17.
1373:0036-8075
1314:0028-0836
1243:BioEssays
1010:1471-0056
956:Cisplatin
936:In cancer
839:bisulfite
711:Hotchkiss
655:Discovery
549:P337+P313
545:P333+P313
533:P302+P352
454:labelling
214:209-058-3
206:EC Number
2506:23061750
2453:29676998
2396:23177740
2310:25968125
2291:24138928
2224:29643443
2140:21376230
2052:20495664
1990:21251613
1933:25675246
1876:21778364
1811:23602153
1754:17713477
1689:10325416
1627:23370418
1619:29033456
1573:15689527
1475:20800313
1440:27588157
1271:10784130
1263:10376011
1228:22344696
1179:18873306
1138:18107446
1018:28555658
899:(5hmC),
809:In vitro
691:cytosine
649:nitrogen
619:cytosine
445:Hazards
74:554-01-8
2514:8775590
2444:5940111
2387:3780611
2335:erratum
2327:erratum
2321:erratum
2282:4015143
2232:4709691
2091:8653676
2043:2873040
1981:3229304
1924:4784441
1867:3495246
1838:Bibcode
1830:Science
1802:3657391
1745:2712830
1716:Bibcode
1524:8065911
1431:5007816
1408:Bibcode
1381:6262918
1353:Bibcode
1345:Science
1330:4236677
1322:2423876
1294:Bibcode
1219:3367185
1026:3393814
951:de novo
946:de novo
867:de novo
863:de novo
820:thymine
790:thymine
741:In vivo
707:picrate
695:Johnson
687:guanine
683:thymine
588:what is
586: (
485:Warning
438:125.131
258:PubChem
140:120387
2539:
2512:
2504:
2496:
2451:
2441:
2433:
2394:
2384:
2376:
2308:
2304:,
2289:
2279:
2271:
2230:
2222:
2214:
2179:
2138:
2130:
2089:
2081:
2050:
2040:
2032:
1988:
1978:
1970:
1931:
1921:
1913:
1874:
1864:
1856:
1809:
1799:
1791:
1752:
1742:
1734:
1708:Nature
1687:
1680:148793
1677:
1669:
1625:
1617:
1609:
1571:
1563:
1522:
1515:310266
1512:
1473:
1438:
1428:
1379:
1371:
1328:
1320:
1312:
1286:Nature
1269:
1261:
1226:
1216:
1177:
1136:
1049:
1024:
1016:
1008:
814:The NH
798:APOBEC
786:uracil
730:uracil
724:using
722:thymus
671:named
583:verify
580:
374:SMILES
232:C02376
123:B00435
115:3DMet
36:Names
2510:S2CID
2331:with
2228:S2CID
1623:S2CID
1326:S2CID
1267:S2CID
1022:S2CID
717:from
661:toxin
617:base
609:is a
339:InChI
271:65040
175:58551
146:ChEBI
87:JSmol
50:)-one
2537:ISBN
2502:PMID
2494:ISSN
2449:PMID
2431:ISSN
2392:PMID
2374:ISSN
2306:PMID
2287:PMID
2269:ISSN
2220:PMID
2212:ISSN
2177:ISSN
2163:2021
2136:PMID
2128:ISSN
2110:Cell
2087:PMID
2079:ISSN
2048:PMID
2030:ISSN
1986:PMID
1968:ISSN
1929:PMID
1911:ISSN
1872:PMID
1854:ISSN
1807:PMID
1789:ISSN
1773:Cell
1750:PMID
1732:ISSN
1685:PMID
1667:ISSN
1615:PMID
1607:ISSN
1569:PMID
1561:ISSN
1520:PMID
1471:PMID
1436:PMID
1377:PMID
1369:ISSN
1318:PMID
1310:ISSN
1259:PMID
1224:PMID
1175:PMID
1134:PMID
1047:ISBN
1014:PMID
1006:ISSN
719:calf
689:and
557:P501
553:P363
541:P321
529:P280
525:P272
521:P264
517:P261
503:H319
499:H317
282:UNII
243:MeSH
223:KEGG
2484:hdl
2476:doi
2439:PMC
2423:doi
2382:PMC
2366:doi
2298:doi
2277:PMC
2259:doi
2204:doi
2167:doi
2118:doi
2114:144
2038:PMC
2022:doi
1976:PMC
1960:doi
1919:PMC
1903:doi
1899:115
1862:PMC
1846:doi
1834:333
1797:PMC
1781:doi
1777:153
1740:PMC
1724:doi
1712:449
1675:PMC
1659:doi
1599:doi
1551:doi
1510:PMC
1502:doi
1463:doi
1426:PMC
1416:doi
1361:doi
1349:212
1302:doi
1290:321
1251:doi
1214:PMC
1206:doi
1165:doi
1161:175
1124:doi
1120:177
1080:doi
1070:".
998:doi
909:TET
766:CpG
759:CpG
734:RNA
715:DNA
615:DNA
452:GHS
308:EPA
261:CID
2565::
2508:.
2500:.
2492:.
2482:.
2472:11
2470:.
2447:.
2437:.
2429:.
2419:10
2417:.
2413:.
2390:.
2380:.
2372:.
2362:49
2360:.
2356:.
2285:.
2275:.
2267:.
2255:14
2253:.
2249:.
2226:.
2218:.
2210:.
2200:19
2198:.
2175:.
2161:.
2157:.
2134:.
2126:.
2112:.
2108:.
2085:.
2075:56
2073:.
2069:.
2046:.
2036:.
2028:.
2016:.
2012:.
1998:^
1984:.
1974:.
1966:.
1956:19
1954:.
1950:.
1927:.
1917:.
1909:.
1897:.
1893:.
1870:.
1860:.
1852:.
1844:.
1832:.
1828:.
1805:.
1795:.
1787:.
1775:.
1771:.
1748:.
1738:.
1730:.
1722:.
1710:.
1706:.
1683:.
1673:.
1665:.
1655:27
1653:.
1649:.
1635:^
1621:.
1613:.
1605:.
1595:19
1593:.
1581:^
1567:.
1559:.
1547:22
1545:.
1541:.
1518:.
1508:.
1498:22
1496:.
1492:.
1469:.
1459:26
1457:.
1434:.
1424:.
1414:.
1404:38
1402:.
1398:.
1375:.
1367:.
1359:.
1347:.
1324:.
1316:.
1308:.
1300:.
1288:.
1265:.
1257:.
1247:21
1245:.
1222:.
1212:.
1202:40
1200:.
1196:.
1173:.
1159:.
1155:.
1132:.
1118:.
1114:.
1076:47
1074:.
1020:.
1012:.
1004:.
994:18
992:.
978:^
845:.
685:,
640:.
555:,
551:,
547:,
543:,
539:,
535:,
531:,
527:,
523:,
519:,
501:,
456::
2555:)
2547:(
2545:.
2516:.
2486::
2478::
2455:.
2425::
2398:.
2368::
2341:)
2339:.
2300::
2293:.
2261::
2234:.
2206::
2183:.
2169::
2142:.
2120::
2093:.
2054:.
2024::
2018:1
1992:.
1962::
1935:.
1905::
1878:.
1848::
1840::
1813:.
1783::
1756:.
1726::
1718::
1691:.
1661::
1629:.
1601::
1575:.
1553::
1526:.
1504::
1477:.
1465::
1442:.
1418::
1410::
1383:.
1363::
1355::
1332:.
1304::
1296::
1273:.
1253::
1230:.
1208::
1181:.
1167::
1140:.
1126::
1086:.
1082::
1055:.
1028:.
1000::
816:2
754:.
578:Y
426:O
423:3
420:N
417:7
414:H
411:5
408:C
310:)
306:(
89:)
48:H
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
