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Nat Rev Mol Cell Biol. 2019 Oct;20(10):573-589. doi: 10.1038/s41580-019-0143-1. Epub 2019 Jul 3.

The roles of DNA, RNA and histone methylation in ageing and cancer.

Author information

1
Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia.
2
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.
3
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
4
Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge, UK. a.bannister@gurdon.cam.ac.uk.
5
Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia. mark.dawson@petermac.org.
6
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia. mark.dawson@petermac.org.
7
Centre for Cancer Research, The University of Melbourne, Melbourne, Australia. mark.dawson@petermac.org.

Abstract

Chromatin is a macromolecular complex predominantly comprising DNA, histone proteins and RNA. The methylation of chromatin components is highly conserved as it helps coordinate the regulation of gene expression, DNA repair and DNA replication. Dynamic changes in chromatin methylation are essential for cell-fate determination and development. Consequently, inherited or acquired mutations in the major factors that regulate the methylation of DNA, RNA and/or histones are commonly observed in developmental disorders, ageing and cancer. This has provided the impetus for the clinical development of epigenetic therapies aimed at resetting the methylation imbalance observed in these disorders. In this Review, we discuss the cellular functions of chromatin methylation and focus on how this fundamental biological process is corrupted in cancer. We discuss methylation-based cancer therapies and provide a perspective on the emerging data from early-phase clinical trial therapies that target regulators of DNA and histone methylation. We also highlight promising therapeutic strategies, including monitoring chromatin methylation for diagnostic purposes and combination epigenetic therapy strategies that may improve immune surveillance in cancer and increase the efficacy of conventional and targeted anticancer drugs.

PMID:
31270442
DOI:
10.1038/s41580-019-0143-1

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