The effect of an intervening promoter nucleosome on gene expression

PLoS One. 2013 May 20;8(5):e63072. doi: 10.1371/journal.pone.0063072. Print 2013.

Abstract

Nucleosomes, which are the basic packaging units of chromatin, are stably positioned in promoters upstream of most stress-inducible genes. These promoter nucleosomes are generally thought to repress gene expression due to exclusion; they prevent transcription factors from accessing their target sites on the DNA. However, the role of promoter nucleosomes that do not directly occlude transcription factor binding sites is not obvious. Here, we varied the stability of a non-occluding nucleosome positioned between a transcription factor binding site and the TATA box region in an inducible yeast promoter and measured downstream gene expression level. We found that gene expression level depends on the occupancy of the non-occluding nucleosome in a non-monotonic manner. We postulated that a non-occluding nucleosome can serve both as a vehicle of and a barrier to chromatin remodeling activity and built a quantitative, nonequilibrium model to explain the observed nontrivial effect of the intervening nucleosome. Our work sheds light on the dual role of nucleosome as a repressor and an activator and expands the standard model of gene expression to include irreversible promoter chromatin transitions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / genetics
  • Acid Phosphatase / metabolism
  • Binding Sites
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Fungal
  • Nucleosomes / genetics*
  • Nucleosomes / metabolism
  • Promoter Regions, Genetic*
  • Protein Binding
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription, Genetic*

Substances

  • DNA-Binding Proteins
  • Nucleosomes
  • PHO4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Acid Phosphatase
  • PHO5 protein, S cerevisiae

Grants and funding

HDK received support from Burroughs Wellcome Fund CASI award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.