Editing Gene expression (section)

===DNA methylation and demethylation in transcriptional regulation===

[[File:DNA methylation.svg|thumb|300px|DNA methylation is the addition of a [[methyl]] group to the DNA that happens at [[cytosine]]. The image shows a cytosine single ring base and a methyl group added on to the 5 carbon. In mammals, DNA methylation occurs almost exclusively at a cytosine that is followed by a [[guanine]].]]

[[DNA methylation]] is a widespread mechanism for epigenetic influence on gene expression and is seen in [[bacteria]] and [[eukaryotes]] and has roles in heritable transcription silencing and transcription regulation. Methylation most often occurs on a cytosine (see Figure). Methylation of cytosine primarily occurs in dinucleotide sequences where a cytosine is followed by a guanine, a [[CpG site]]. The number of [[CpG site]]s in the human genome is about 28 million.<ref name="pmid26932361">{{cite journal | vauthors = Lövkvist C, Dodd IB, Sneppen K, Haerter JO | title = DNA methylation in human epigenomes depends on local topology of CpG sites | journal = Nucleic Acids Research | volume = 44 | issue = 11 | pages = 5123–5132 | date = June 2016 | pmid = 26932361 | pmc = 4914085 | doi = 10.1093/nar/gkw124 }}</ref> Depending on the type of cell, about 70% of the CpG sites have a methylated cytosine.<ref name="Jabbari2004">{{cite journal | vauthors = Jabbari K, Bernardi G | title = Cytosine methylation and CpG, TpG (CpA) and TpA frequencies | journal = Gene | volume = 333 | pages = 143–149 | date = May 2004 | pmid = 15177689 | doi = 10.1016/j.gene.2004.02.043 }}</ref>

Methylation of cytosine in DNA has a major role in regulating gene expression. Methylation of CpGs in a promoter region of a gene usually represses gene transcription<ref name="pmid17334365">{{cite journal | vauthors = Weber M, Hellmann I, Stadler MB, Ramos L, Pääbo S, Rebhan M, Schübeler D | title = Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome | journal = Nature Genetics | volume = 39 | issue = 4 | pages = 457–466 | date = April 2007 | pmid = 17334365 | doi = 10.1038/ng1990 | s2cid = 22446734 }}</ref> while methylation of CpGs in the body of a gene increases expression.<ref name="pmid25263941">{{cite journal | vauthors = Yang X, Han H, De Carvalho DD, Lay FD, Jones PA, Liang G | title = Gene body methylation can alter gene expression and is a therapeutic target in cancer | journal = Cancer Cell | volume = 26 | issue = 4 | pages = 577–590 | date = October 2014 | pmid = 25263941 | pmc = 4224113 | doi = 10.1016/j.ccr.2014.07.028 }}</ref> [[TET enzymes]] play a central role in demethylation of methylated cytosines. Demethylation of CpGs in a gene promoter by [[TET enzymes|TET enzyme]] activity increases transcription of the gene.<ref name="pmid24108092">{{cite journal | vauthors = Maeder ML, Angstman JF, Richardson ME, Linder SJ, Cascio VM, Tsai SQ, Ho QH, Sander JD, Reyon D, Bernstein BE, Costello JF, Wilkinson MF, Joung JK | title = Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins | journal = Nature Biotechnology | volume = 31 | issue = 12 | pages = 1137–1142 | date = December 2013 | pmid = 24108092 | pmc = 3858462 | doi = 10.1038/nbt.2726 }}</ref>