The epigenetic basis of cellular heterogeneity

Nat Rev Genet. 2021 Apr;22(4):235-250. doi: 10.1038/s41576-020-00300-0. Epub 2020 Nov 26.

Abstract

Single-cell sequencing-based methods for profiling gene transcript levels have revealed substantial heterogeneity in expression levels among morphologically indistinguishable cells. This variability has important functional implications for tissue biology and disease states such as cancer. Mapping of epigenomic information such as chromatin accessibility, nucleosome positioning, histone tail modifications and enhancer-promoter interactions in both bulk-cell and single-cell samples has shown that these characteristics of chromatin state contribute to expression or repression of associated genes. Advances in single-cell epigenomic profiling methods are enabling high-resolution mapping of chromatin states in individual cells. Recent studies using these techniques provide evidence that variations in different aspects of chromatin organization collectively define gene expression heterogeneity among otherwise highly similar cells.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Cell Lineage / genetics
  • Chromatin / genetics*
  • Computational Biology
  • DNA Methylation / genetics*
  • Epigenesis, Genetic / genetics*
  • Genetic Heterogeneity*
  • Histones / genetics
  • Humans
  • Promoter Regions, Genetic / genetics
  • Regulatory Sequences, Nucleic Acid / genetics
  • Sequence Analysis, DNA

Substances

  • Chromatin
  • Histones