Condensin-Dependent Chromatin Compaction Represses Transcription Globally during Quiescence

Mol Cell. 2019 Feb 7;73(3):533-546.e4. doi: 10.1016/j.molcel.2018.11.020. Epub 2018 Dec 27.

Abstract

Quiescence is a stress-resistant state in which cells reversibly exit the cell cycle and suspend most processes. Quiescence is essential for stem cell maintenance, and its misregulation is implicated in tumor formation. One of the hallmarks of quiescent cells is highly condensed chromatin. Because condensed chromatin often correlates with transcriptional silencing, it has been hypothesized that chromatin compaction represses transcription during quiescence. However, the technology to test this model by determining chromatin structure within cells at gene resolution has not previously been available. Here, we use Micro-C XL to map chromatin contacts at single-nucleosome resolution genome-wide in quiescent Saccharomyces cerevisiae cells. We describe chromatin domains on the order of 10-60 kilobases that, only in quiescent cells, are formed by condensin-mediated loops. Condensin depletion prevents the compaction of chromatin within domains and leads to widespread transcriptional de-repression. Finally, we demonstrate that condensin-dependent chromatin compaction is conserved in quiescent human fibroblasts.

Keywords: Micro-C; chromatin boundary; chromatin condensation; chromatin domains; condensin; quiescence; transcriptional repression.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Binding Sites
  • Cell Proliferation
  • Cells, Cultured
  • Cellular Senescence*
  • Chromatin / genetics*
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fibroblasts / enzymology*
  • Gene Expression Regulation, Fungal
  • Humans
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Protein Binding
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Time Factors
  • Transcription, Genetic*

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Saccharomyces cerevisiae Proteins
  • condensin complexes
  • Adenosine Triphosphatases