Structural basis of nucleosome transcription mediated by Chd1 and FACT

Nat Struct Mol Biol. 2021 Apr;28(4):382-387. doi: 10.1038/s41594-021-00578-6. Epub 2021 Apr 12.

Abstract

Efficient transcription of RNA polymerase II (Pol II) through nucleosomes requires the help of various factors. Here we show biochemically that Pol II transcription through a nucleosome is facilitated by the chromatin remodeler Chd1 and the histone chaperone FACT when the elongation factors Spt4/5 and TFIIS are present. We report cryo-EM structures of transcribing Saccharomyces cerevisiae Pol II-Spt4/5-nucleosome complexes with bound Chd1 or FACT. In the first structure, Pol II transcription exposes the proximal histone H2A-H2B dimer that is bound by Spt5. Pol II has also released the inhibitory DNA-binding region of Chd1 that is poised to pump DNA toward Pol II. In the second structure, Pol II has generated a partially unraveled nucleosome that binds FACT, which excludes Chd1 and Spt5. These results suggest that Pol II progression through a nucleosome activates Chd1, enables FACT binding and eventually triggers transfer of FACT together with histones to upstream DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • CHD1 protein, S cerevisiae
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • FACT protein, S cerevisiae
  • High Mobility Group Proteins
  • Histones
  • Multiprotein Complexes
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Transcriptional Elongation Factors
  • SPT5 transcriptional elongation factor
  • RNA Polymerase II