Multiple sequence-specific factors generate the nucleosome-depleted region on CLN2 promoter

Mol Cell. 2011 May 20;42(4):465-76. doi: 10.1016/j.molcel.2011.03.028.

Abstract

Nucleosome-depleted regions (NDRs) are ubiquitous on eukaryotic promoters. The formation of many NDRs cannot be readily explained by previously proposed mechanisms. Here, we carry out a focused study on a physiologically important NDR in the yeast CLN2 promoter (CLN2pr). We show that this NDR does not result from intrinsically unfavorable histone-DNA interaction. Instead, we identified eight conserved factor binding sites, including that of Reb1, Mcm1, and Rsc3, that cause the local nucleosome depletion. These nucleosome-depleting factors (NDFs) work redundantly, and simultaneously mutating all their binding sites eliminates CLN2pr NDR. The loss of the NDR induces unreliable "on/off" expression in individual cell cycles, but in the presence of the NDR, NDFs have little direct effect on transcription. We present bioinformatic evidence that the formation of many NDRs across the genome involves multiple NDFs. Our findings also provide significant insight into the composition and spatial organization of functional promoters.

Publication types

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

MeSH terms

  • Base Sequence
  • Binding Sites / genetics
  • Computational Biology
  • Cyclins / genetics*
  • Gene Expression Regulation, Fungal*
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*
  • Promoter Regions, Genetic*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics*

Substances

  • CLN2 protein, S cerevisiae
  • Cyclins
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins