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DNA Methylation in Mammals

By Dr Ananya Mandal, MD

DNA methylation is essential to healthy mammalian development and function. The process is involved with several important processes which include:

  • Genomic imprinting
  • Carcinogenesis
  • Suppression of repetitive elements
  • Suppression of retroviral gene expression

What happens?

DNA methylation refers to the addition of a methyl (CH3) group to the cytosine or guanine nucleotide. This methyl group may be added to the fifth carbon atom of the cytosine base or the sixth nitrogen atom of the adenine base. In adult human somatic cells, DNA methylation usually occurs at a CpG site, which is a sequence of DNA where cytosine is located next to guanine.

Among mammals, around 60% to 90% of all CpGs are methylated. Methylated C residues lose an amine group to give T residues. The CpG dinucleotides therefore mutate into TpG dinucleotides. Unmethylated CpG residues can also lose an amine group, to give a uracil residue, but this mutation is quickly recognized and fixed.

Unmethylated CpGs are often found in groups called CpG islands, located at the 5’ regulatory region of genes. Cancer and other diseases processes often begin when these islands undergo hypermethylation, leading to transcriptional silencing, which can be passed on to daughter cells during cell division.

Alteration of the DNA methylation therefore forms an important first step in the development of cancer.

Studies have shown that genes with a promoter region that contains a high concentration of 5-methylcytosine are transcriptionally silent. Aberrant methylation of DNA has been associated with an increased rate of malignancy. DNA hypermethylation is linked to the activation of genes and DNA hypomethylation has been associated with the development of cancer through various mechanisms.

Reviewed by , BSc

Further Reading

Last Updated: May 6, 2014

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