FACT is recruited to the +1 nucleosome of transcribed genes and spreads in a Chd1-dependent manner

Mol Cell. 2021 Sep 2;81(17):3542-3559.e11. doi: 10.1016/j.molcel.2021.07.010. Epub 2021 Aug 10.


The histone chaperone FACT occupies transcribed regions where it plays prominent roles in maintaining chromatin integrity and preserving epigenetic information. How it is targeted to transcribed regions, however, remains unclear. Proposed models include docking on the RNA polymerase II (RNAPII) C-terminal domain (CTD), recruitment by elongation factors, recognition of modified histone tails, and binding partially disassembled nucleosomes. Here, we systematically test these and other scenarios in Saccharomyces cerevisiae and find that FACT binds transcribed chromatin, not RNAPII. Through a combination of high-resolution genome-wide mapping, single-molecule tracking, and mathematical modeling, we propose that FACT recognizes the +1 nucleosome, as it is partially unwrapped by the engaging RNAPII, and spreads to downstream nucleosomes aided by the chromatin remodeler Chd1. Our work clarifies how FACT interacts with genes, suggests a processive mechanism for FACT function, and provides a framework to further dissect the molecular mechanisms of transcription-coupled histone chaperoning.

Keywords: Chd1; FACT; Pob3; RNA polymerase II; Spt16; chromatin remodeling; histone chaperone; mathematical modeling; nucleosome unwrapping; single-molecule tracking.

Publication types

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

MeSH terms

  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Histone Chaperones / genetics
  • Histones / genetics
  • Histones / metabolism
  • Molecular Chaperones / metabolism
  • Nucleosomes / metabolism
  • Protein Binding
  • RNA Polymerase II / metabolism
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription, Genetic / genetics*
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism*


  • CHD1 protein, S cerevisiae
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • FACT protein, S cerevisiae
  • High Mobility Group Proteins
  • Histone Chaperones
  • Histones
  • Molecular Chaperones
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Transcriptional Elongation Factors
  • RNA Polymerase II