Interplay between chromatin marks in development and disease

Nat Rev Genet. 2022 Mar;23(3):137-153. doi: 10.1038/s41576-021-00416-x. Epub 2021 Oct 4.

Abstract

DNA methylation (DNAme) and histone post-translational modifications (PTMs) have important roles in transcriptional regulation. Although many reports have characterized the functions of such chromatin marks in isolation, recent genome-wide studies reveal surprisingly complex interactions between them. Here, we focus on the interplay between DNAme and methylation of specific lysine residues on the histone H3 tail. We describe the impact of genetic perturbation of the relevant methyltransferases in the mouse on the landscape of chromatin marks as well as the transcriptome. In addition, we discuss the specific neurodevelopmental growth syndromes and cancers resulting from pathogenic mutations in the human orthologues of these genes. Integrating these observations underscores the fundamental importance of crosstalk between DNA and histone H3 methylation in development and disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly / physiology
  • DNA Methylation / genetics*
  • Disease / genetics*
  • Growth and Development / genetics*
  • Histones / metabolism
  • Humans
  • Mice
  • Protein Processing, Post-Translational

Substances

  • Chromatin
  • Histones