Editing Epigenetics (section)

===DNA methylation===
{{further|Methylation}}
[[DNA methylation]] frequently occurs in repeated sequences, and helps to suppress the expression and mobility of '[[transposable elements]]':<ref name="slotkin2007">{{cite journal | vauthors = Slotkin RK, Martienssen R | title = Transposable elements and the epigenetic regulation of the genome | journal = Nature Reviews. Genetics | volume = 8 | issue = 4 | pages = 272–85 | date = April 2007 | pmid = 17363976 | doi = 10.1038/nrg2072 | s2cid = 9719784 }}</ref> Because [[5-methylcytosine]] can be spontaneously deaminated (replacing nitrogen by oxygen) to [[thymidine]], CpG sites are frequently mutated and become rare in the genome, except at [[CpG islands]] 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 independent [[DNA methyltransferase]]s, DNMT1, DNMT3A, and DNMT3B, the loss of any of which is lethal in mice.<ref name="li92">{{cite journal | vauthors = Li E, Bestor TH, Jaenisch R | title = Targeted mutation of the DNA methyltransferase gene results in embryonic lethality | journal = Cell | volume = 69 | issue = 6 | pages = 915–26 | date = June 1992 | pmid = 1606615 | doi = 10.1016/0092-8674(92)90611-F | s2cid = 19879601 }}</ref> DNMT1 is the most abundant methyltransferase in somatic cells,<ref name="robertson99">{{cite journal | vauthors = Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA | title = The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors | journal = Nucleic Acids Research | volume = 27 | issue = 11 | pages = 2291–8 | date = June 1999 | pmid = 10325416 | pmc = 148793 | doi = 10.1093/nar/27.11.2291 }}</ref> localizes to replication foci,<ref name="leonhardt92">{{cite journal | vauthors = Leonhardt H, Page AW, Weier HU, Bestor TH | title = A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei | journal = Cell | volume = 71 | issue = 5 | pages = 865–73 | date = November 1992 | pmid = 1423634 | doi = 10.1016/0092-8674(92)90561-P | s2cid = 5995820 | url = https://epub.ub.uni-muenchen.de/5003/1/003.pdf }}</ref> has a 10–40-fold preference for hemimethylated DNA and interacts with the [[proliferating cell nuclear antigen]] (PCNA).<ref name="chuang97">{{cite journal | vauthors = Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF | title = Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1 | journal = Science | volume = 277 | issue = 5334 | pages = 1996–2000 | date = September 1997 | pmid = 9302295 | doi = 10.1126/science.277.5334.1996 }}</ref>

By preferentially modifying hemimethylated DNA, DNMT1 transfers patterns of methylation to a newly synthesized strand after [[DNA replication]], and therefore is often referred to as the 'maintenance' methyltransferase.<ref name="robertson00">{{cite journal | vauthors = Robertson KD, Wolffe AP | title = DNA methylation in health and disease | journal = Nature Reviews. Genetics | volume = 1 | issue = 1 | pages = 11–9 | date = October 2000 | pmid = 11262868 | doi = 10.1038/35049533 | s2cid = 1915808 }}</ref> DNMT1 is essential for proper embryonic development, imprinting and X-inactivation.<ref name="li92" /><ref name="li93">{{cite journal | vauthors = Li E, Beard C, Jaenisch R | title = Role for DNA methylation in genomic imprinting | journal = Nature | volume = 366 | issue = 6453 | pages = 362–5 | date = November 1993 | pmid = 8247133 | doi = 10.1038/366362a0 | bibcode = 1993Natur.366..362L | s2cid = 4311091 }}</ref> 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.<ref>{{cite journal | vauthors = Viens A, Mechold U, Brouillard F, Gilbert C, Leclerc P, Ogryzko V | title = Analysis of human histone H2AZ deposition in vivo argues against its direct role in epigenetic templating mechanisms | journal = Molecular and Cellular Biology | volume = 26 | issue = 14 | pages = 5325–35 | date = July 2006 | pmid = 16809769 | pmc = 1592707 | doi = 10.1128/MCB.00584-06 }}</ref> 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 ([[Structural inheritance|structural]]) heritable states.<ref name="pmid18419815">{{cite journal | vauthors = Ogryzko VV | title = Erwin Schroedinger, Francis Crick and epigenetic stability | journal = Biology Direct | volume = 3 | pages = 15 | date = April 2008 | pmid = 18419815 | pmc = 2413215 | doi = 10.1186/1745-6150-3-15 | doi-access = free }}</ref>