In biochemistry, methylation more specifically refers to the replacement of a hydrogen atom with the methyl group.
In biological systems, methylation is catalyzed by enzymes; such methylation can be involved in modification of heavy metals, regulation of gene expression, regulation of protein function, and RNA metabolism. Methylation of heavy metals can also occur outside of biological systems. Chemical methylation of tissue samples is also one method for reducing certain histological staining artifacts.
DNA methylation in vertebrates typically occurs at CpG sites (cytosine-phosphate-guanine sites; that is, where a cytosine is directly followed by a guanine in the DNA sequence); this methylation results in the conversion of the cytosine to 5-methylcytosine. The formation of Me-CpG is catalyzed by the enzyme DNA methyltransferase. CpG sites are uncommon in vertebrate genomes but are often found at higher density near vertebrate gene promoters where they are collectively referred to as CpG islands. The methylation state of these CpG sites can have a major impact on gene activity/expression.
Protein methylation typically takes place on arginine or lysine amino acid residues in the protein sequence. Arginine can be methylated once (monomethylated arginine) or twice, with either both methyl groups on one terminal nitrogen (asymmetric dimethylated arginine) or one on both nitrogens (symmetric dimethylated arginine) by peptidylarginine methyltransferases (PRMTs). Lysine can be methylated once, twice or three times by lysine methyltransferases. Protein methylation has been most well studied in the histones. The transfer of methyl groups from S-adenosyl methionine to histones is catalyzed by enzymes known as histone methyltransferases. Histones which are methylated on certain residues can act epigenetically to repress or activate gene expression. Protein methylation is one type of post-translational modification.
Neoplasia is characterized by "methylation imbalance" where genome-wide hypomethylation is accompanied by localized hypermethylation and an increase in expression of DNA methyltransferase. The overall methylation state in a cell might also be a precipitating factor in carcinogenesis as evidence suggests that genome-wide hypomethylation can lead to chromosome instability and increased mutation rates. The methylation state of some genes can be used as a biomarker for tumorigenesis. For instance, hypermethylation of the pi-class glutathione S-transferase gene (GSTP1) appears to be a promising diagnostic indicator of prostate cancer.
In cancer, the dynamics of genetic and epigenetic gene silencing are very different. Somatic genetic mutation leads to a block in the production of functional protein from the mutant allele. If a selective advantage is conferred to the cell, the cells expand clonally to give rise to a tumor in which all cells lack the capacity to produce protein. In contrast, epigenetically mediated gene silencing occurs gradually. It begins with a subtle decrease in transcription, fostering a decrease in protection of the CpG island from the spread of flanking heterochromatin and methylation into the island. This loss results in gradual increases of individual CpG sites, which vary between copies of the same gene in different cells.
Alternatively, the methylation may involve use of nucleophilic methyl compounds such as methyllithium (CH3Li) or Grignard reagents (CH3MgX). For example, CH3Li will methylate acetone, adding across the carbonyl (C=O) to give the lithium alkoxide of tert-butanol:
DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines.(Research)(Report)
Jan 20, 2011; Authors: Jordana T Bell (corresponding author) [1,3]; Athma A Pai ; Joseph K Pickrell ; Daniel J Gaffney [1,2]; Roger...