Molecular Biology

Erasing DNA Methyl Marks

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Science  22 Oct 2004:
Vol. 306, Issue 5696, pp. 579
DOI: 10.1126/science.306.5696.579c

Methylation of DNA plays an important role in the epigenetic regulation of gene expression, including preventing the activation and spread of invading nucleic acids in the genome, such as transposable elements. These patterns of 5-methyl C (5meC) in DNA undergo a genome-wide reprogramming in early embryos and primordial germ cells, yet the mechanism by which the methyl marks are removed independently of DNA replication is not known.

Morgan et al. now show that the enzyme Activation-Induced Cytidine Deaminase (Aid), which together with other family members is known to deaminate C residues in DNA and/or RNA, is also able to deaminate methylated C residues in single-stranded DNA, resulting in a mismatched pairing of G against the transformed T. This G:T pair can be repaired back to the Watson and Crick G:C pair, with the loss of the methyl group, or the mutant T can be fixed in the sequence. Provocatively, Aid and its relative Apobec1 are expressed in the specific tissues and at the time when 5meC reprogramming occurs. Furthermore, the genes for both are located in close proximity to, and coexpressed with, a cluster of genes involved in tissue pluripotency, leading the authors to speculate that Aid and Apobec1 may, through their 5meC deaminase activity, play a role in epigenetic reprogramming. — GR

J. Biol. Chem. 10.1074/jbc.M407695200 (2004).

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