The interplay between DNA and histone methylation: molecular mechanisms and disease implications

EMBO Rep. 2021 May 5;22(5):e51803. doi: 10.15252/embr.202051803. Epub 2021 Apr 12.

Abstract

Methylation of cytosine in CpG dinucleotides and histone lysine and arginine residues is a chromatin modification that critically contributes to the regulation of genome integrity, replication, and accessibility. A strong correlation exists between the genome-wide distribution of DNA and histone methylation, suggesting an intimate relationship between these epigenetic marks. Indeed, accumulating literature reveals complex mechanisms underlying the molecular crosstalk between DNA and histone methylation. These in vitro and in vivo discoveries are further supported by the finding that genes encoding DNA- and histone-modifying enzymes are often mutated in overlapping human diseases. Here, we summarize recent advances in understanding how DNA and histone methylation cooperate to maintain the cellular epigenomic landscape. We will also discuss the potential implication of these insights for understanding the etiology of, and developing biomarkers and therapies for, human congenital disorders and cancers that are driven by chromatin abnormalities.

Keywords: DNA methylation; cancer; chromatin; developmental disorder; histone methylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chromatin / genetics
  • DNA
  • DNA Methylation
  • Epigenesis, Genetic
  • Histones* / genetics
  • Histones* / metabolism
  • Humans
  • Methylation
  • Protein Processing, Post-Translational*

Substances

  • Chromatin
  • Histones
  • DNA