Editing Promoter (genetics) (section)

==CpG islands in promoters==
{{main|Regulation of transcription in cancer}}

In humans, about 70% of promoters located near the transcription start site of a gene (proximal promoters) contain a [[CpG site#CpG islands|CpG island]].<ref name="pmid16432200">{{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 = 1412–1417 | date = January 2006 | pmid = 16432200 | pmc = 1345710 | doi = 10.1073/pnas.0510310103 | doi-access = free | bibcode = 2006PNAS..103.1412S }}</ref><ref name="pmid21576262">{{cite journal | vauthors = Deaton AM, Bird A | title = CpG islands and the regulation of transcription | journal = Genes & Development | volume = 25 | issue = 10 | pages = 1010–1022 | date = May 2011 | pmid = 21576262 | pmc = 3093116 | doi = 10.1101/gad.2037511 }}</ref>   CpG islands are generally 200 to 2000 base pairs long, have a C:G [[base pair]] content >50%, and have regions of [[DNA]] where a [[cytosine]] [[nucleotide]] is followed by a [[guanine]] nucleotide and this occurs frequently in the linear [[DNA sequence|sequence]] of [[Base pair|base]]s along its [[Directionality (molecular biology)|5' → 3' direction]].

Distal promoters also frequently contain CpG islands, such as the promoter of the DNA repair gene ''[[ERCC1]]'', where the CpG island-containing promoter is located about 5,400 nucleotides upstream of the coding region of the ''ERCC1'' gene.<ref name="pmid19626585">{{cite journal | vauthors = Chen HY, Shao CJ, Chen FR, Kwan AL, Chen ZP | title = Role of ERCC1 promoter hypermethylation in drug resistance to cisplatin in human gliomas | journal = International Journal of Cancer | volume = 126 | issue = 8 | pages = 1944–1954 | date = April 2010 | pmid = 19626585 | doi = 10.1002/ijc.24772 | doi-access = free }}</ref>  CpG islands also occur frequently in promoters for [[Noncoding DNA#Noncoding functional RNA|functional noncoding RNAs]] such as [[microRNA]]s.

===Methylation of CpG islands stably silences genes===

In humans, DNA methylation occurs at the 5' position of the pyrimidine ring of the cytosine residues within [[CpG site]]s to form [[5-methylcytosine]]s.  The presence of multiple methylated CpG sites in CpG islands of promoters causes stable silencing of genes.<ref name=Bird />  Silencing of a gene may be initiated by other mechanisms, but this is often followed by methylation of CpG sites in the promoter CpG island to cause the stable silencing of the gene.<ref name=Bird />

===Promoter CpG hyper/hypo-methylation in cancer===

Generally, in progression to cancer, hundreds of genes are [[Regulation of transcription in cancer#Transcription silencing/activation in cancers|silenced or activated]].  Although silencing of some genes in cancers occurs by mutation, a large proportion of carcinogenic gene silencing is a result of altered DNA methylation (see [[DNA methylation in cancer]]).  DNA methylation causing silencing in cancer typically occurs at multiple [[CpG site]]s in the [[CpG site#CpG island|CpG island]]s that are present in the promoters of protein coding genes.

Altered expressions of [[microRNA]]s also silence or activate many genes in progression to cancer (see [[MicroRNA#cancer|microRNAs in cancer]]).  Altered microRNA expression occurs through [[Regulation of transcription in cancer#Transcription silencing/activation in cancers|hyper/hypo-methylation]] of [[CpG site]]s in [[CpG site#CpG island|CpG island]]s in promoters controlling transcription of the [[microRNA]]s.

Silencing of DNA repair genes through methylation of CpG islands in their promoters appears to be especially important in progression to cancer (see [[DNA methylation in cancer#Likely role of hypermethylation of DNA repair genes in cancer|methylation of DNA repair genes in cancer]]).