Methylation

Methylation refers to the replacement of a molecule or atom by a methyl (−CH3) group. Various types of methylation are defined based upon the atom or molecule that is replaced. In genetics, methylation may refer to the silencing of one of the X chromosomes in females by adding a methyl groups to its cytosine bases by an enzyme called DNA methyltransferase. In biochemistry, methylation is the replacement of a hydrogen atom with a methyl group. Methylation reactions are usually catalyzed by enzymes.

Methylation serves specific purpose in systems; for example, it may be used to modify the structure of heavy metals, regulate the expression of genes, regulate the function of proteins, and also regulate the metabolism of RNA. There are two basic types of methylation: chemical and biological methylation.

Chemical methylation is studied in the area of organic chemistry, where the term alkylation is used to define the addition of a −CH3 group. Alkylation is done using electrophilic (electron loving) compounds such as dimethyl sulfate and iodomethane, which react in a nucleophilic substitution. For example, ethers may be produced by methylation of alkoxides, and ketones may be produced by methylation of ketone enolates.

Biological methylation occurs in various ways. In epigenetic inheritance, methylation can occur as DNA methylation or protein methylation. In DNA methylation, there is an addition of a methyl group to a cytosine residue, causing cytosine to become 5-methylcytosine. DNA methylation occurs at CpG sites, that is, sites where a cytosine is immediately in front of a guanine. This type of methylation controls gene expression or activity. In protein methylation, a lysine amino acid or an arginine residue is methylated [Page 1123]in the reaction. Arginine may be methylated once or twice, and lysine may be methylated once, twice or three times. Histones can also be methylated by an enzyme called histone methyltransferase, which transfers methyl groups from S-adenosyl methionine to the histone. Protein methylation is also used to control gene expression by activating or deactivating a gene.

Eukaryotic embryos also undergo methylation. Eukaryotic DNA is unmethylated from fertilization to 8-cell stage. It then undergoes de novo methylation from the 8-cell stage to morula, during which epigenetic information is modified and added to the genome. Methylation is complete by blastula stage. If embryonic methylation doesn't occur, the embryo dies. Methylation continues to occur in the postnatal development and plays an important role in the interaction of gene expression and environmental factors.

Methylation plays an important role in tumor formation. Tumors begin with abnormal localized hypermethylation, genome-wide hypomethylation, and increased expression of DNA methyltransferase. Research shows that genome-wide hypomethylation leads to increased mutation rates and instability of chromosomes. Furthermore, hypermethylation is one of the symptoms seen in prostate cancer.

Bacteria also use methylation as a tool for self-de-fense. Bacteria protect its DNA by methylation of adenosine bases. Foreign DNA that enters the bacteria remains unmethylated, thus, prone to destruction by the bacteria's restriction enzymes.