The language of chromatin modification in human cancers

Nat Rev Cancer. 2021 Jul;21(7):413-430. doi: 10.1038/s41568-021-00357-x. Epub 2021 May 17.

Abstract

The genetic information of human cells is stored in the context of chromatin, which is subjected to DNA methylation and various histone modifications. Such a 'language' of chromatin modification constitutes a fundamental means of gene and (epi)genome regulation, underlying a myriad of cellular and developmental processes. In recent years, mounting evidence has demonstrated that miswriting, misreading or mis-erasing of the modification language embedded in chromatin represents a common, sometimes early and pivotal, event across a wide range of human cancers, contributing to oncogenesis through the induction of epigenetic, transcriptomic and phenotypic alterations. It is increasingly clear that cancer-related metabolic perturbations and oncohistone mutations also directly impact chromatin modification, thereby promoting cancerous transformation. Phase separation-based deregulation of chromatin modulators and chromatin structure is also emerging to be an important underpinning of tumorigenesis. Understanding the various molecular pathways that underscore a misregulated chromatin language in cancer, together with discovery and development of more effective drugs to target these chromatin-related vulnerabilities, will enhance treatment of human malignancies.

Publication types

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

MeSH terms

  • Chromatin / chemistry
  • Chromatin / metabolism*
  • DNA Methylation
  • Histone Code*
  • Histone-Lysine N-Methyltransferase / chemistry
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Mutation
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Neoplasms / genetics*

Substances

  • Chromatin
  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • DOT1L protein, human
  • Histone-Lysine N-Methyltransferase