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DNA methylation: old dog, new tricks?

Nature Structural & Molecular Biology volume 21, pages 949–954 (2014)Cite this article

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Abstract

DNA methylation is an epigenetic modification that is generally associated with repression of transcription initiation at CpG-island promoters. Here we argue that, on the basis of recent high-throughput genomic and proteomic screenings, DNA methylation can also have different outcomes, including activation of transcription. This is evidenced by the fact that transcription factors can interact with methylated DNA sequences. Furthermore, in certain cellular contexts, genes containing methylated promoters are highly transcribed. Interestingly, this uncoupling between methylated DNA and repression of transcription seems to be particularly evident in germ cells and pluripotent cells. Thus, contrary to previous assumptions, DNA methylation is not exclusively associated with repression of transcription initiation.

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Figure 1: Models of transcriptional regulation by DNA methylation.
Figure 2: Schematic representation of the different classes of DNA-binding domains that have been implicated in C, mC and hmC binding: CXXC15,34,36, MBD34,36,53,54, SRA34,36,54,58, forkhead box or winged helix34,36, C2H2 zinc finger22,34,36,37,40,44,83, helix-turn-helix (homeobox)34,36, basic leucine zipper36,41 and helix-loop-helix8,37,84.

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Acknowledgements

We would like to thank O. Bogdanovic, A. Brinkman, S. Kloet and A. Smits for critical reading of the manuscript. The Vermeulen laboratory is supported by grants from the Netherlands Organisation for Scientific Research (NWO-VIDI (no. 864.09.003) and Cancer Genomics Netherlands) and a European Research Council starting grant (no. 309384).

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  1. Department of Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands

    Cornelia G Spruijt & Michiel Vermeulen

  2. Department of Molecular Biology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands

    Michiel Vermeulen

  3. Cancer Genomics Netherlands, the Netherlands

    Michiel Vermeulen

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Correspondence to Michiel Vermeulen.

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Spruijt, C., Vermeulen, M. DNA methylation: old dog, new tricks?. Nat Struct Mol Biol 21, 949–954 (2014). https://doi.org/10.1038/nsmb.2910

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