Resolution of transcription-induced hexasome-nucleosome complexes by Chd1 and FACT

Mol Cell. 2024 Sep 19;84(18):3423-3437.e8. doi: 10.1016/j.molcel.2024.08.022. Epub 2024 Sep 12.

Abstract

To maintain the nucleosome organization of transcribed genes, ATP-dependent chromatin remodelers collaborate with histone chaperones. Here, we show that at the 5' ends of yeast genes, RNA polymerase II (RNAPII) generates hexasomes that occur directly adjacent to nucleosomes. The resulting hexasome-nucleosome complexes are then resolved by Chd1. We present two cryoelectron microscopy (cryo-EM) structures of Chd1 bound to a hexasome-nucleosome complex before and after restoration of the missing inner H2A/H2B dimer by FACT. Chd1 uniquely interacts with the complex, positioning its ATPase domain to shift the hexasome away from the nucleosome. In the absence of the inner H2A/H2B dimer, its DNA-binding domain (DBD) packs against the ATPase domain, suggesting an inhibited state. Restoration of the dimer by FACT triggers a rearrangement that displaces the DBD and stimulates Chd1 remodeling. Our results demonstrate how chromatin remodelers interact with a complex nucleosome assembly and suggest how Chd1 and FACT jointly support transcription by RNAPII.

Keywords: Chd1; FACT; chromatin remodeling; hexasome-nucleosome complexes; transcription.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Chromatin Assembly and Disassembly*
  • Cryoelectron Microscopy*
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • High Mobility Group Proteins* / genetics
  • High Mobility Group Proteins* / metabolism
  • Histones* / genetics
  • Histones* / metabolism
  • Models, Molecular
  • Nucleosomes* / genetics
  • Nucleosomes* / metabolism
  • Nucleosomes* / ultrastructure
  • Protein Binding
  • RNA Polymerase II* / genetics
  • RNA Polymerase II* / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism
  • Transcription, Genetic*
  • Transcriptional Elongation Factors* / chemistry
  • Transcriptional Elongation Factors* / genetics
  • Transcriptional Elongation Factors* / metabolism

Substances

  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • CHD1 protein, S cerevisiae
  • Transcriptional Elongation Factors
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • FACT protein, S cerevisiae
  • RNA Polymerase II
  • Histones
  • Adenosine Triphosphatases