The transcription factor Atf1 lowers the transition barrier for nucleosome-mediated establishment of heterochromatin

Cell Rep. 2022 May 17;39(7):110828. doi: 10.1016/j.celrep.2022.110828.


Transcription factors can exert opposite effects depending on the chromosomal context. The fission yeast transcription factor Atf1 both activates numerous genes in response to stresses and mediates heterochromatic gene silencing in the mating-type region. Investigating this context dependency, we report here that the establishment of silent heterochromatin in the mating-type region occurs at a reduced rate in the absence of Atf1 binding. Quantitative modeling accounts for the observed establishment profiles by a combinatorial recruitment of histone-modifying enzymes: locally by Atf1 at two binding sites and over the whole region by dynamically appearing heterochromatic nucleosomes, a source of which is the RNAi-dependent cenH element. In the absence of Atf1 binding, the synergy is lost, resulting in a slow rate of heterochromatin formation. The system shows how DNA-binding proteins can influence local nucleosome states and thereby potentiate long-range positive feedback on histone-modification reactions to enable heterochromatin formation over large regions in a context-dependent manner.

Keywords: CP: Molecular biology; epigenetics; fission yeast; gene silencing; heterochromatin; histone modifications; mathematical modeling; position effects; positive feedback; single-cell studies; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 1 / genetics
  • Activating Transcription Factor 1 / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Heterochromatin / metabolism
  • Histones / metabolism
  • Nucleosomes / metabolism
  • Phosphoproteins / metabolism
  • Schizosaccharomyces pombe Proteins* / metabolism
  • Schizosaccharomyces* / genetics
  • Schizosaccharomyces* / metabolism
  • Transcription Factors / metabolism


  • Activating Transcription Factor 1
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • Histones
  • Nucleosomes
  • Phosphoproteins
  • Schizosaccharomyces pombe Proteins
  • Transcription Factors
  • atf1 protein, S pombe