Abstract
Cytosine methylation is a DNA modification generally associated with transcriptional silencing. Factors that regulate methylation have been linked to human disease, yet how they contribute to malignances remains largely unknown. Genomic maps of DNA methylation have revealed unexpected dynamics at gene regulatory regions, including active demethylation by TET proteins at binding sites for transcription factors. These observations indicate that the underlying DNA sequence largely accounts for local patterns of methylation. As a result, this mark is highly informative when studying gene regulation in normal and diseased cells, and it can potentially function as a biomarker. Although these findings challenge the view that methylation is generally instructive for gene silencing, several open questions remain, including how methylation is targeted and recognized and in what context it affects genome readout.
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Acknowledgements
I apologize to colleagues, whose work I could not cite or only discuss in a limited context owing to space limitations. I thank in particular P. Ginno and further T. Baubec., M. Lorincz and N. Thomae for critical input on the manuscript. Work in my laboratory is supported by the Novartis research foundation, the European Union (NoE EpiGeneSys FP7- HEALTH-2010-257082 and the Blueprint consortium FP7-282510), the European Research Council (EpiGePlas), the SNF Sinergia programme and the Swiss Initiative in Systems Biology (RTD Cell Plasticity).
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Schübeler, D. Function and information content of DNA methylation. Nature 517, 321–326 (2015). https://doi.org/10.1038/nature14192
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DOI: https://doi.org/10.1038/nature14192
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