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Citation
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HERO ID
7356282
Reference Type
Journal Article
Subtype
Review
Title
The roles of DNA, RNA and histone methylation in ageing and cancer
Author(s)
Michalak, EM; Burr, ML; Bannister, AJ; Dawson, MA
Year
2019
Is Peer Reviewed?
1
Journal
Nature Reviews. Molecular Cell Biology
ISSN:
1471-0072
EISSN:
1471-0080
Volume
20
Issue
10
Page Numbers
573-589
Language
English
PMID
31270442
DOI
10.1038/s41580-019-0143-1
Web of Science Id
WOS:000487247100004
URL
http://www.nature.com/articles/s41580-019-0143-1
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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.
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