Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement
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 geno...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/54449 |
| _version_ | 1811180570839875584 |
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| author | Avinash B Patel Camille M Moore Basil J Greber Jie Luo Stefan A Zukin Jeff Ranish Eva Nogales |
| author_facet | Avinash B Patel Camille M Moore Basil J Greber Jie Luo Stefan A Zukin Jeff Ranish Eva Nogales |
| author_sort | Avinash B Patel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:04:18Z |
| format | Article |
| id | doaj.art-d9d11fbfbfc24d01ba3adfdb5fb2b76f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:04:18Z |
| publishDate | 2019-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-d9d11fbfbfc24d01ba3adfdb5fb2b76f2022-12-22T04:32:40ZengeLife Sciences Publications LtdeLife2050-084X2019-12-01810.7554/eLife.54449Architecture of the chromatin remodeler RSC and insights into its nucleosome engagementAvinash B Patel0https://orcid.org/0000-0001-9140-8375Camille M Moore1Basil J Greber2https://orcid.org/0000-0001-9379-7159Jie Luo3Stefan A Zukin4Jeff Ranish5Eva Nogales6https://orcid.org/0000-0001-9816-3681Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States; Molecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, United StatesMolecular and Cell Biology Department, University of California, Berkeley, Berkeley, United StatesMolecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, United States; California Institute for Quantitative Biology (QB3), University of California, Berkeley, Berkeley, United StatesThe Institute for Systems Biology, Seattle, United StatesChemistry Department, University of California, Berkeley, Berkeley, United StatesThe Institute for Systems Biology, Seattle, United StatesMolecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, United States; Molecular and Cell Biology Department, University of California, Berkeley, Berkeley, United States; California Institute for Quantitative Biology (QB3), University of California, Berkeley, Berkeley, United States; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United StatesEukaryotic 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.https://elifesciences.org/articles/54449cryo-EMchromatintranscriptionchromatin remodeling |
| spellingShingle | Avinash B Patel Camille M Moore Basil J Greber Jie Luo Stefan A Zukin Jeff Ranish Eva Nogales Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement eLife cryo-EM chromatin transcription chromatin remodeling |
| title | Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement |
| title_full | Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement |
| title_fullStr | Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement |
| title_full_unstemmed | Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement |
| title_short | Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement |
| title_sort | architecture of the chromatin remodeler rsc and insights into its nucleosome engagement |
| topic | cryo-EM chromatin transcription chromatin remodeling |
| url | https://elifesciences.org/articles/54449 |
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