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DNA METABOLISM

5mC: what goes on must come off

Nature Reviews Molecular Cell Biology volume 23, page 306 (2022)Cite this article

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In the mammalian genome, cytosine can undergo covalent modifications, leading to increased genetic and epigenetic diversity. The most well-studied cytosine modification is the addition of a methyl group at the 5 position to generate 5-methylcytosine (5mC). Almost all 5mC is found in CpG dinucleotides, where it has a crucial role in a number of physiological processes such as genomic imprinting, X-chromosome inactivation and transposon repression. Mammalian DNA methyltransferases, which convert C to 5mC, were first identified in 1982. Since then, their catalytic mechanism and co-factors have been fully elucidated.

Nonetheless, how this epigenetic modification is reversed remained a mystery. The dynamicity of 5mC levels during primordial germ cell reprogramming implicated both passive and active means of demethylation, and although decreased DNA methyltransferase 1 activity during DNA replication can result in passive demethylation, the agents responsible for active demethylation remained unknown.

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References

Original article

  • Tahiliani, M. et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930–935 (2009)

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  1. Genomic Medicine & Department of Urology, Cleveland Clinic, Cleveland, OH, USA

    Angela H. Ting & Byron H. Lee

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  1. Angela H. Ting
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  2. Byron H. Lee
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Correspondence to Angela H. Ting or Byron H. Lee.

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Ting, A.H., Lee, B.H. 5mC: what goes on must come off. Nat Rev Mol Cell Biol 23, 306 (2022). https://doi.org/10.1038/s41580-022-00469-8

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