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

Journal article

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.

Authors: Jeronimo, C; Angel, A; Nguyen, VQ; Kim, JM; Poitras, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Molecular Cell
• Volume: 81
• Issue: 17
• Pages: 3542-3559.e11
• Publication date: 2021-08-10
• Acceptance date: 2021-07-12
• DOI: 10.1016/j.molcel.2021.07.010
• EISSN: 1097-4164
• ISSN: 1097-2765
• Pmid: 34380014
• Language: English
• Keywords: FFR; chromatin assembly and disassembly; non-histone chromosomal proteins; Saccharomyces cerevisiae; high mobility group proteins; RNA polymerase II; Saccharomyces cerevisiae proteins; DNA-binding proteins; chromatin; transcriptional elongation factors; protein binding; nucleosomes; histones; molecular chaperones; histone chaperones; genetic transcription