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DNA methylation
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=== CpG islands === {{main|CpG islands}} In mammals, the only exception for this global CpG depletion resides in a specific category of GC- and CpG-rich sequences termed CpG islands that are generally unmethylated and therefore retained the expected CpG content.<ref>{{cite journal | vauthors = Bird AP | title = CpG-rich islands and the function of DNA methylation | journal = Nature | volume = 321 | issue = 6067 | pages = 209β213 | date = 1986-05-15 | pmid = 2423876 | doi = 10.1038/321209a0 | s2cid = 4236677 | author-link = Adrian Bird | bibcode = 1986Natur.321..209B }}</ref> CpG islands are usually defined as regions with: 1) a length greater than 200bp, 2) a G+C content greater than 50%, 3) a ratio of observed to expected CpG greater than 0.6, although other definitions are sometimes used.<ref>{{cite journal | vauthors = Gardiner-Garden M, Frommer M | title = CpG islands in vertebrate genomes | journal = Journal of Molecular Biology | volume = 196 | issue = 2 | pages = 261β282 | date = July 1987 | pmid = 3656447 | doi = 10.1016/0022-2836(87)90689-9 }}</ref> Excluding repeated sequences, there are around 25,000 CpG islands in the human genome, 75% of which being less than 850bp long.<ref name="Human Genome Sequencing and Analysis" /> They are major regulatory units and around 50% of CpG islands are located in gene promoter regions, while another 25% lie in gene bodies, often serving as alternative promoters. Reciprocally, around 60-70% of human genes have a CpG island in their promoter region.<ref>{{cite journal | vauthors = Illingworth RS, Gruenewald-Schneider U, Webb S, Kerr AR, James KD, Turner DJ, Smith C, Harrison DJ, Andrews R, Bird AP | display-authors = 6 | title = Orphan CpG islands identify numerous conserved promoters in the mammalian genome | journal = PLOS Genetics | volume = 6 | issue = 9 | pages = e1001134 | date = September 2010 | pmid = 20885785 | pmc = 2944787 | doi = 10.1371/journal.pgen.1001134 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Saxonov S, Berg P, Brutlag DL | title = A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 5 | pages = 1412β1417 | date = January 2006 | pmid = 16432200 | pmc = 1345710 | doi = 10.1073/pnas.0510310103 | doi-access = free | bibcode = 2006PNAS..103.1412S }}</ref> The majority of CpG islands are constitutively unmethylated and enriched for permissive [[Histone modification|chromatin modification]] such as [[H3K4]] methylation. In somatic tissues, only 10% of CpG islands are methylated, the majority of them being located in intergenic and intragenic regions.{{cn|date=March 2024}}
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