Establishment and Maintenance of Chromatin Architecture Are Promoted Independently of Transcription by the Histone Chaperone FACT and H3-K56 Acetylation in Saccharomyces cerevisiae

Genetics. 2019 Mar;211(3):877-892. doi: 10.1534/genetics.118.301853. Epub 2019 Jan 24.


FACT (FAcilitates Chromatin Transcription/Transactions) is a histone chaperone that can destabilize or assemble nucleosomes. Acetylation of histone H3-K56 weakens a histone-DNA contact that is central to FACT activity, suggesting that this modification could affect FACT functions. We tested this by asking how mutations of H3-K56 and FACT affect nucleosome reorganization activity in vitro, and chromatin integrity and transcript output in vivo Mimics of unacetylated or permanently acetylated H3-K56 had different effects on FACT activity as expected, but the same mutations had surprisingly similar effects on global transcript levels. The results are consistent with emerging models that emphasize FACT's importance in establishing global chromatin architecture prior to transcription, promoting transitions among different states as transcription profiles change, and restoring chromatin integrity after it is disturbed. Optimal FACT activity required the availability of both modified and unmodified states of H3-K56. Perturbing this balance was especially detrimental for maintaining repression of genes with high nucleosome occupancy over their promoters and for blocking antisense transcription at the +1 nucleosome. The results reveal a complex collaboration between H3-K56 modification status and multiple FACT functions, and support roles for nucleosome reorganization by FACT before, during, and after transcription.

Keywords: FACT; chromatin; histone chaperone.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Chromatin Assembly and Disassembly*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Histone Chaperones / genetics
  • Histone Chaperones / metabolism*
  • Histone Code*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism*


  • DNA-Binding Proteins
  • FACT protein, S cerevisiae
  • High Mobility Group Proteins
  • Histone Chaperones
  • Saccharomyces cerevisiae Proteins
  • Transcriptional Elongation Factors

Associated data

  • figshare/10.25386/genetics.7586207