Single cell analysis pushes the boundaries of TAD formation and function

Curr Opin Genet Dev. 2020 Apr;61:25-31. doi: 10.1016/j.gde.2020.03.005. Epub 2020 Apr 14.

Abstract

Eukaryotic genomes encode genetic information in their linear sequence, but appropriate expression of their genes requires chromosomes to fold into complex three-dimensional structures. Fueled by a growing collection of sequencing and imaging-based technologies, studies have uncovered a hierarchy of DNA interactions, from small chromatin loops that connect genes and enhancers to larger topologically associated domains (TADs) and compartments. However, despite the remarkable conservation of these organizational features, we have a very limited understanding of how this organization influences gene expression. This issue is further complicated in the context of single-cell heterogeneity, as has recently been revealed at both the level of gene activation and chromatin topology. Here, we provide a perspective on recent studies that address cell-to-cell variability and the relationship between structural heterogeneity and gene expression. We propose that transcription is regulated by variable 3D structures driven by at least two independent and partially redundant mechanisms. Collectively, this may provide flexibility to transcriptional regulation at the level of individual cells as well as reproducibility across whole tissues.

Publication types

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

MeSH terms

  • Chromatin / genetics*
  • Chromatin / ultrastructure
  • Chromosomes / genetics*
  • Chromosomes / ultrastructure
  • Evolution, Molecular*
  • Gene Expression Regulation
  • Genome, Human / genetics
  • Humans
  • Single-Cell Analysis*

Substances

  • Chromatin