DNA Methylation

One mechanism of gene regulation in eukaryotes is the methylation of DNA. The vast majority of this involves methylation of the Cytosine in the dinucleotide CpG. (The p is used to indicate the phosphodiester bond.) Methylation can be designated by mCpG. Note that this sequence is self-complementary, so the other strand also contains a CpG and generally both are methylated at the same time.

Although most CpG dinucleotides in a genome are not methylated at a given time, methylation can be used as a method of down-regulating genes. This is generally accomplished by CpG islands.

CpG Island: This refers to a genome region, usually about 1 to 2 kb in length, that has a high frequency of CpG dinucleotides. There are roughly 30,000 CpG islands within the human genome. These islands usually occur near transcription start sites and are involved in gene regulation via the methylation of the Cytosine bases in the CpG dinucleotides. Methylation of CpG dinucleotides within the CpG islands is generally associated with the silencing or down-regulation of nearby genes.

This provides eukaryotes with an efficient manner of silencing a gene simply by methylating a nearby CpG island. This is particularly noticeable in the inactive X chromosome in female mammals, which is extensively methylated.

Methylation and chromatin remodeling: Evidence indicates that methylated DNA influences gene expression by recruiting proteins that modify histones resulting in chromatin remodeling. Unmethylated CpG islands are apparently associated with methylated histones (such as H3K4me3), while methylation of CpGs seems to lead to histone demethylation. However, the relationship between CpG methylation and histone modification is not well understood.

DNA methylation is also involved in imprinting.