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In Chemistry, Methylation is the addition of a methyl group to a substrate.

In Epigenetics, Methylation can refer to the addition of a methyl group to a cytosine residue of DNA to convert it to 5-methylcytosine or the addition of a methyl group or groups to arginine or lysine amino acids in a protein.

Methylation of DNA occurs at any CpG sites, which are sequences of DNA where cytosine lies next to guanine. The process of methylation is mediated by an enzyme known as DNA methyltransferase. CpG sites are quite rare in a eukaryotic genome except in regions near the promoter of a eukaryotic gene. These regions are known as CpG islands, and the state of methylation of these CpG sites are critical for gene activity/expression.

In early development (fertilisation to 8-cell stage), the eukaryotic genome is demethylated. From the 8-cell stage to the morula, de novo methylation of the genome occurs, modifying and adding epigenetic information to the genome. By blastula stage, the methylation is complete. This process is referred to as "epigenetic reprogramming". The importance of methylation was shown in knockout mutants without DNA methyltransferase. All the resulting embryos died at the morula stage.

The pattern of methylation has recently become an important topic for research. Studies have found that in normal tissue, methylation of a gene is mainly localised to the coding region, which is CpG poor. In contrast, the promoter region of the gene is unmethylated, despite a high density of CpG islands in the region.

Interestingly, in cancer cells, methylation is very high even in the promoter region, raising interest in the role of methylation in the induction of cancerous properties. Furthermore, the pattern of methylation has been shown to be a reliable marker of cancerous tissue, with a heavily methylated gene found in 90% or more patients with prostate cancer.

Additionally, adenosine methylation is part of the restriction modification system of many bacteria. Bacterial DNAs are methylated periodically throughout the genome, and foreign DNAs (which are not methylated in this manner) that are introduced into the cell are degraded by restriction enzymes. Bacteria protect themselves from infection by bacteria viruses, called bacteriophage or phage, through this system.

Methylation can occur on the arginine and lysine residues of proteins. Methylation of protein 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 in epigenetically to repress or activate "gene" expression.