Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement
- University of California, Berkeley, United States
- The Institute for Systems Biology, United States
- Lawrence Berkeley National Laboratory, United States
Abstract
Eukaryotic DNA is packaged into nucleosome arrays, which are repositioned by chromatin remodeling complexes to control DNA accessibility. The Saccharomyces cerevisiae RSC (Remodeling the Structure of Chromatin) complex, a member of the SWI/SNF chromatin remodeler family, plays critical roles in genome maintenance, transcription, and DNA repair. Here we report cryo-electron microscopy (cryo-EM) and crosslinking mass spectrometry (CLMS) studies of yeast RSC complex and show that RSC is composed of a rigid tripartite core and two flexible lobes. The core structure is scaffolded by an asymmetric Rsc8 dimer and built with the evolutionarily conserved subunits Sfh1, Rsc6, Rsc9 and Sth1. The flexible ATPase lobe, composed of helicase subunit Sth1, Arp7, Arp9 and Rtt102, is anchored to this core by the N-terminus of Sth1. Our cryo-EM analysis of RSC bound to a nucleosome core particle shows that in addition to the expected nucleosome-Sth1 interactions, RSC engages histones and nucleosomal DNA through one arm of the core structure, composed of the Rsc8 SWIRM domains, Sfh1 and Npl6. Our findings provide structural insights into the conserved assembly process for all members of the SWI/SNF family of remodelers, and illustrate how RSC selects, engages, and remodels nucleosomes.
Data availability
The cryo-EM maps and coordinate models have been deposited in the Electron Microscopy Data Bank with the accession codes EMD-21107 (RSC core), EMD-21105 (head lobe multibody), EMD-21103 (body lobe multibody), EMD-21098 (arm lobe multibody), EMD-21106 (head lobe classified), EMD-21102 (body lobe classified), EMD-21104 (arm lobe classified), EMD-21114 (RSC-NCP locked) and EMD-21110 (RSC-NCP swiveled) and in the Protein Data Bank with the accession codes PDB-6V8O (RSC core) and PDB-6V92 (RSC-NCP).
Article and author information
Author details
Funding
National Institutes of Health (U24GM129547)
- Eva Nogales
National Institute of General Medical Sciences (R01-GM63072)
- Eva Nogales
National Institute of General Medical Sciences (R35-GM127018)
- Eva Nogales
National Institute of General Medical Sciences (R01- GM110064)
- Jeff Ranish
National Institute of General Medical Sciences (R01-HL133678)
- Jeff Ranish
Howard Hughes Medical Institute
- Eva Nogales
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Patel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 6,068
- views
-
- 884
- downloads
-
- 78
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Citations by DOI
-
- 78
- citations for umbrella DOI https://doi.org/10.7554/eLife.54449
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement
eLife 8:e54449.
https://doi.org/10.7554/eLife.54449
