A dynamic interplay of nucleosome and Msn2 binding regulates kinetics of gene activation and repression following stress

Nucleic Acids Res. 2014 May;42(9):5468-82. doi: 10.1093/nar/gku176. Epub 2014 Mar 5.

Abstract

The transcription factor Msn2 mediates a significant proportion of the environmental stress response, in which a common cohort of genes changes expression in a stereotypic fashion upon exposure to any of a wide variety of stresses. We have applied genome-wide chromatin immunoprecipitation and nucleosome profiling to determine where Msn2 binds under stressful conditions and how that binding affects, and is affected by, nucleosome positioning. We concurrently determined the effect of Msn2 activity on gene expression following stress and demonstrated that Msn2 stimulates both activation and repression. We found that some genes responded to both intermittent and continuous Msn2 nuclear occupancy while others responded only to continuous occupancy. Finally, these studies document a dynamic interplay between nucleosomes and Msn2 such that nucleosomes can restrict access of Msn2 to its canonical binding sites while Msn2 can promote reposition, expulsion and recruitment of nucleosomes to alter gene expression. This interplay may allow the cell to discriminate between different types of stress signaling.

Publication types

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

MeSH terms

  • Base Sequence
  • Binding Sites
  • Chromosome Mapping
  • Consensus Sequence
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Fungal*
  • Gene Silencing
  • Genes, Fungal
  • Kinetics
  • Nucleosomes / metabolism*
  • Oxidative Stress*
  • Promoter Regions, Genetic
  • Protein Binding
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Analysis, DNA
  • Transcription Factors / metabolism*
  • Transcriptional Activation

Substances

  • DNA-Binding Proteins
  • MSN2 protein, S cerevisiae
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors