Back to Search
Start Over
Structural insights into histone exchange by human SRCAP complex
- Source :
- Cell Discovery, Vol 10, Iss 1, Pp 1-18 (2024)
- Publication Year :
- 2024
- Publisher :
- Nature Publishing Group, 2024.
-
Abstract
- Abstract Histone variant H2A.Z is found at promoters and regulates transcription. The ATP-dependent chromatin remodeler SRCAP complex (SRCAP-C) promotes the replacement of canonical histone H2A–H2B dimer with H2A.Z–H2B dimer. Here, we determined structures of human SRCAP-C bound to H2A-containing nucleosome at near-atomic resolution. The SRCAP subunit integrates a 6-subunit actin-related protein (ARP) module and an ATPase-containing motor module. The ATPase-associated ARP module encircles half of the nucleosome along the DNA and may restrain net DNA translocation, a unique feature of SRCAP-C. The motor module adopts distinct nucleosome binding modes in the apo (nucleotide-free), ADP-bound, and ADP-BeFx-bound states, suggesting that ATPase-driven movement destabilizes H2A–H2B by unwrapping the entry DNA and pulls H2A–H2B out of nucleosome through the ZNHIT1 subunit. Structure-guided chromatin immunoprecipitation sequencing analysis confirmed the requirement of H2A-contacting ZNHIT1 in maintaining H2A.Z occupancy on the genome. Our study provides structural insights into the mechanism of H2A-H2A.Z exchange mediated by SRCAP-C.
Details
- Language :
- English
- ISSN :
- 20565968
- Volume :
- 10
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Discovery
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.6d94dae7ca964fd5bce56b5fd5594940
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41421-023-00640-1