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Do short, frequent DNA sequence motifs mould the epigenome?

Nature Reviews Molecular Cell Biology volume 17, pages 257–262 (2016)Cite this article

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Abstract

'Epigenome' refers to the panoply of chemical modifications borne by DNA and its associated proteins that locally affect genome function. Epigenomic patterns are thought to be determined by external constraints resulting from development, disease and the environment, but DNA sequence is also a potential influence. We propose that domains of relatively uniform DNA base composition may modulate the epigenome through cell type-specific proteins that recognize short, frequent sequence motifs. Differential recruitment of epigenomic modifiers may adjust gene expression in multigene blocks as an alternative to tuning the activity of each gene separately, thus simplifying gene expression programming.

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Figure 1: Differences in DNA methylation in a region of the human brain reflect base composition.
Figure 2: Long-range depletion of DNA methylation in cancer.
Figure 3: Does sharply changing base composition in CpG island (CGI) shores cause variable DNA methylation?
Figure 4: Small differences in base composition cause large differences in the frequency of AT-run motifs.

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Acknowledgements

This work was supported by a Programme grant (091580) and Centre Core Grant (092076) from the Wellcome Trust to A.B.. T.Q. is an EU Marie Curie Fellow. The authors thank Kashyap Chhatbar for help with bioinformatic analysis.

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  1. Timo Quante and Adrian Bird are at the Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, The King's Buildings, Edinburgh EH9 3BF, UK.,

    Timo Quante & Adrian Bird

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Correspondence to Adrian Bird.

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Quante, T., Bird, A. Do short, frequent DNA sequence motifs mould the epigenome?. Nat Rev Mol Cell Biol 17, 257–262 (2016). https://doi.org/10.1038/nrm.2015.31

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