Contrasting roles of the RSC and ISW1/CHD1 chromatin remodelers in RNA polymerase II elongation and termination

Genome Res. 2019 Mar;29(3):407-417. doi: 10.1101/gr.242032.118. Epub 2019 Jan 25.

Abstract

Most yeast genes have a nucleosome-depleted region (NDR) at the promoter and an array of regularly spaced nucleosomes phased relative to the transcription start site. We have examined the interplay between RSC (a conserved essential SWI/SNF-type complex that determines NDR size) and the ISW1, CHD1, and ISW2 nucleosome spacing enzymes in chromatin organization and transcription, using isogenic strains lacking all combinations of these enzymes. The contributions of these remodelers to chromatin organization are largely combinatorial, distinct, and nonredundant, supporting a model in which the +1 nucleosome is positioned by RSC and then used as a reference nucleosome by the spacing enzymes. Defective chromatin organization correlates with altered RNA polymerase II (Pol II) distribution. RSC-depleted cells exhibit low levels of elongating Pol II and high levels of terminating Pol II, consistent with defects in both termination and initiation, suggesting that RSC facilitates both. Cells lacking both ISW1 and CHD1 show the opposite Pol II distribution, suggesting elongation and termination defects. These cells have extremely disrupted chromatin, with high levels of closely packed dinucleosomes involving the second (+2) nucleosome. We propose that ISW1 and CHD1 facilitate Pol II elongation by separating closely packed nucleosomes.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Chromatin Assembly and Disassembly*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Fungal
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • RNA Polymerase II / genetics*
  • RNA Polymerase II / metabolism
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Elongation, Genetic*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription Termination, Genetic*

Substances

  • CHD1 protein, S cerevisiae
  • DNA-Binding Proteins
  • ISWI protein
  • Nucleosomes
  • RSC complex, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • RNA Polymerase II
  • Adenosine Triphosphatases
  • ISW1 protein, S cerevisiae