The chromatin remodeler Chd1 regulates cohesin in budding yeast and humans

Sci Rep. 2019 Jun 20;9(1):8929. doi: 10.1038/s41598-019-45263-3.

Abstract

Chd1 is a chromatin remodeler that is involved in nucleosome positioning and transcription. Deletion of CHD1 is a frequent event in prostate cancer. The Structural Maintenance of Chromosome (SMC) complex cohesin mediates long-range chromatin interactions and is involved in maintaining genome stability. We provide new evidence that Chd1 is a regulator of cohesin. In the yeast S. cerevisiae, Chd1 is not essential for viability. We show that deletion of the gene leads to a defect in sister chromatid cohesion and in chromosome morphology. Chl1 is a non-essential DNA helicase that has been shown to regulate cohesin loading. Surprisingly, co-deletion of CHD1 and CHL1 results in an additive cohesion defect but partial suppression of the chromosome structure phenotype. We found that the cohesin regulator Pds5 is overexpressed when Chd1 and Chl1 are deleted. However, Pds5 expression is reduced to wild type levels when both genes are deleted. Finally, we show a correlation in the expression of CHD1 and cohesin genes in prostate cancer patients. Furthermore, we show that overexpression of cohesin subunits is correlated with the aggressiveness of the tumor. The biological roles of the interplay between Chd1, Chl1 and SMCs are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / physiology*
  • Chromatin Assembly and Disassembly / physiology*
  • Chromosomal Proteins, Non-Histone / physiology*
  • Cohesins
  • DNA Helicases / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Humans
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / physiology*
  • Sister Chromatid Exchange
  • Transcription Factors / genetics

Substances

  • CHD1 protein, S cerevisiae
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • PDS5B protein, human
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • DNA Helicases
  • CHD1 protein, human