Histone Recycling by FACT and Spt6 during Transcription Prevents the Scrambling of Histone Modifications

Cell Rep. 2019 Jul 30;28(5):1206-1218.e8. doi: 10.1016/j.celrep.2019.06.097.


Genomic DNA is framed by additional layers of information, referred to as the epigenome. Epigenomic marks such as DNA methylation, histone modifications, and histone variants are concentrated on specific genomic sites, where they can both instruct and reflect gene expression. How this information is maintained, notably in the face of transcription, is not completely understood. Specifically, the extent to which modified histones themselves are retained through RNA polymerase II passage is unclear. Here, we show that several histone modifications are mislocalized when the transcription-coupled histone chaperones FACT or Spt6 are disrupted in Saccharomyces cerevisiae. In the absence of functional FACT or Spt6, transcription generates nucleosome loss, which is partially compensated for by the increased activity of non-transcription-coupled histone chaperones. The random incorporation of transcription-evicted modified histones scrambles epigenomic information. Our work highlights the importance of local recycling of modified histones by FACT and Spt6 during transcription in the maintenance of the epigenomic landscape.

Keywords: FACT; Saccharomyces cerevisiae; Spt6; epigenetic landscape; histone chaperone; histone exchange; histone mark; histone modification; histone recycling; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Histone Chaperones / genetics
  • Histone Chaperones / metabolism*
  • Histones / genetics
  • Histones / metabolism*
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Protein Processing, Post-Translational*
  • 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
  • Histones
  • Nucleosomes
  • SPT6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcriptional Elongation Factors