Yeast heterochromatin stably silences only weak regulatory elements by altering burst duration

Cell Rep. 2024 Apr 23;43(4):113983. doi: 10.1016/j.celrep.2024.113983. Epub 2024 Mar 21.

Abstract

Transcriptional silencing in Saccharomyces cerevisiae involves the generation of a chromatin state that stably represses transcription. Using multiple reporter assays, a diverse set of upstream activating sequence enhancers and core promoters were investigated for their susceptibility to silencing. We show that heterochromatin stably silences only weak and stress-induced regulatory elements but is unable to stably repress housekeeping gene regulatory elements, and the partial repression of these elements did not result in bistable expression states. Permutation analysis of enhancers and promoters indicates that both elements are targets of repression. Chromatin remodelers help specific regulatory elements to resist repression, most probably by altering nucleosome mobility and changing transcription burst duration. The strong enhancers/promoters can be repressed if silencer-bound Sir1 is increased. Together, our data suggest that the heterochromatic locus has been optimized to stably silence the weak mating-type gene regulatory elements but not strong housekeeping gene regulatory sequences.

Keywords: CP: Molecular biology; Sir1; UAS enhancer; chromatin; core promoter; heterochromatin; nucleosomes; silencing; transcription; transcription burst.

Publication types

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

MeSH terms

  • Enhancer Elements, Genetic / genetics
  • Gene Expression Regulation, Fungal*
  • Gene Silencing*
  • Heterochromatin* / genetics
  • Heterochromatin* / metabolism
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Promoter Regions, Genetic* / genetics
  • Regulatory Sequences, Nucleic Acid / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism

Substances

  • Heterochromatin
  • Saccharomyces cerevisiae Proteins
  • Nucleosomes