Cryo-EM structure of SWI/SNF complex bound to a nucleosome

Yan Han; Alexis A. Reyes; Sara Malik; Yuan He

doi:10.1038/s41586-020-2087-1

Cryo-EM structure of SWI/SNF complex bound to a nucleosome

Yan Han, Alexis A. Reyes, Sara Malik, Yuan He^*

^*Corresponding author for this work

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

108 Scopus citations

Abstract

The chromatin-remodelling complex SWI/SNF is highly conserved and has critical roles in various cellular processes, including transcription and DNA-damage repair^1,2. It hydrolyses ATP to remodel chromatin structure by sliding and evicting histone octamers^3–8, creating DNA regions that become accessible to other essential factors. However, our mechanistic understanding of the remodelling activity is hindered by the lack of a high-resolution structure of complexes from this family. Here we report the cryo-electron microscopy structure of Saccharomyces cerevisiae SWI/SNF bound to a nucleosome, at near-atomic resolution. In the structure, the actin-related protein (Arp) module is sandwiched between the ATPase and the rest of the complex, with the Snf2 helicase-SANT associated (HSA) domain connecting all modules. The body contains an assembly scaffold composed of conserved subunits Snf12 (also known as SMARCD or BAF60), Snf5 (also known as SMARCB1, BAF47 or INI1) and an asymmetric dimer of Swi3 (also known as SMARCC, BAF155 or BAF170). Another conserved subunit, Swi1 (also known as ARID1 or BAF250), resides in the core of SWI/SNF, acting as a molecular hub. We also observed interactions between Snf5 and the histones at the acidic patch, which could serve as an anchor during active DNA translocation. Our structure enables us to map and rationalize a subset of cancer-related mutations in the human SWI/SNF complex and to propose a model for how SWI/SNF recognizes and remodels the +1 nucleosome to generate nucleosome-depleted regions during gene activation⁹.

Original language	English (US)
Pages (from-to)	452-455
Number of pages	4
Journal	Nature
Volume	579
Issue number	7799
DOIs	https://doi.org/10.1038/s41586-020-2087-1
State	Published - Mar 19 2020

Funding

Acknowledgements We thank J. Remis for assistance with microscope operation and data collection and J. Pattie for computer support; A. Rosenzweig, I. Radhakrishnan and S. Fishbain for helpful discussion and comments on the manuscript; the staff at the Structural Biology Facility of Northwestern University for technical support. This work was supported by a Cornew Innovation Award from the Chemistry of Life Processes Institute at Northwestern University (to Y. He), a Catalyst Award by the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust (to Y. He), an Institutional Research Grant from the American Cancer Society (IRG-15-173-21 to Y. He), an H Foundation Core Facility Pilot Project Award (to Y. He). Y. He is supported by NIGMS grant R01GM135651, NCI grant P01CA092584 and a Pilot Project Award from NCI grant U54CA193419. Y. Han is a recipient of the Chicago Biomedical Consortium Postdoctoral Research Grant. A.A.R. is supported by the Molecular Biophysics Training Program from NIGMS/NIH (5T32 GM008382).

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10.1038/s41586-020-2087-1

Cite this

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title = "Cryo-EM structure of SWI/SNF complex bound to a nucleosome",

abstract = "The chromatin-remodelling complex SWI/SNF is highly conserved and has critical roles in various cellular processes, including transcription and DNA-damage repair1,2. It hydrolyses ATP to remodel chromatin structure by sliding and evicting histone octamers3–8, creating DNA regions that become accessible to other essential factors. However, our mechanistic understanding of the remodelling activity is hindered by the lack of a high-resolution structure of complexes from this family. Here we report the cryo-electron microscopy structure of Saccharomyces cerevisiae SWI/SNF bound to a nucleosome, at near-atomic resolution. In the structure, the actin-related protein (Arp) module is sandwiched between the ATPase and the rest of the complex, with the Snf2 helicase-SANT associated (HSA) domain connecting all modules. The body contains an assembly scaffold composed of conserved subunits Snf12 (also known as SMARCD or BAF60), Snf5 (also known as SMARCB1, BAF47 or INI1) and an asymmetric dimer of Swi3 (also known as SMARCC, BAF155 or BAF170). Another conserved subunit, Swi1 (also known as ARID1 or BAF250), resides in the core of SWI/SNF, acting as a molecular hub. We also observed interactions between Snf5 and the histones at the acidic patch, which could serve as an anchor during active DNA translocation. Our structure enables us to map and rationalize a subset of cancer-related mutations in the human SWI/SNF complex and to propose a model for how SWI/SNF recognizes and remodels the +1 nucleosome to generate nucleosome-depleted regions during gene activation9.",

author = "Yan Han and Reyes, {Alexis A.} and Sara Malik and Yuan He",

note = "Funding Information: Acknowledgements We thank J. Remis for assistance with microscope operation and data collection and J. Pattie for computer support; A. Rosenzweig, I. Radhakrishnan and S. Fishbain for helpful discussion and comments on the manuscript; the staff at the Structural Biology Facility of Northwestern University for technical support. This work was supported by a Cornew Innovation Award from the Chemistry of Life Processes Institute at Northwestern University (to Y. He), a Catalyst Award by the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust (to Y. He), an Institutional Research Grant from the American Cancer Society (IRG-15-173-21 to Y. He), an H Foundation Core Facility Pilot Project Award (to Y. He). Y. He is supported by NIGMS grant R01GM135651, NCI grant P01CA092584 and a Pilot Project Award from NCI grant U54CA193419. Y. Han is a recipient of the Chicago Biomedical Consortium Postdoctoral Research Grant. A.A.R. is supported by the Molecular Biophysics Training Program from NIGMS/NIH (5T32 GM008382). Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

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AU - He, Yuan

N1 - Funding Information: Acknowledgements We thank J. Remis for assistance with microscope operation and data collection and J. Pattie for computer support; A. Rosenzweig, I. Radhakrishnan and S. Fishbain for helpful discussion and comments on the manuscript; the staff at the Structural Biology Facility of Northwestern University for technical support. This work was supported by a Cornew Innovation Award from the Chemistry of Life Processes Institute at Northwestern University (to Y. He), a Catalyst Award by the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust (to Y. He), an Institutional Research Grant from the American Cancer Society (IRG-15-173-21 to Y. He), an H Foundation Core Facility Pilot Project Award (to Y. He). Y. He is supported by NIGMS grant R01GM135651, NCI grant P01CA092584 and a Pilot Project Award from NCI grant U54CA193419. Y. Han is a recipient of the Chicago Biomedical Consortium Postdoctoral Research Grant. A.A.R. is supported by the Molecular Biophysics Training Program from NIGMS/NIH (5T32 GM008382). Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2020/3/19

Y1 - 2020/3/19

N2 - The chromatin-remodelling complex SWI/SNF is highly conserved and has critical roles in various cellular processes, including transcription and DNA-damage repair1,2. It hydrolyses ATP to remodel chromatin structure by sliding and evicting histone octamers3–8, creating DNA regions that become accessible to other essential factors. However, our mechanistic understanding of the remodelling activity is hindered by the lack of a high-resolution structure of complexes from this family. Here we report the cryo-electron microscopy structure of Saccharomyces cerevisiae SWI/SNF bound to a nucleosome, at near-atomic resolution. In the structure, the actin-related protein (Arp) module is sandwiched between the ATPase and the rest of the complex, with the Snf2 helicase-SANT associated (HSA) domain connecting all modules. The body contains an assembly scaffold composed of conserved subunits Snf12 (also known as SMARCD or BAF60), Snf5 (also known as SMARCB1, BAF47 or INI1) and an asymmetric dimer of Swi3 (also known as SMARCC, BAF155 or BAF170). Another conserved subunit, Swi1 (also known as ARID1 or BAF250), resides in the core of SWI/SNF, acting as a molecular hub. We also observed interactions between Snf5 and the histones at the acidic patch, which could serve as an anchor during active DNA translocation. Our structure enables us to map and rationalize a subset of cancer-related mutations in the human SWI/SNF complex and to propose a model for how SWI/SNF recognizes and remodels the +1 nucleosome to generate nucleosome-depleted regions during gene activation9.

AB - The chromatin-remodelling complex SWI/SNF is highly conserved and has critical roles in various cellular processes, including transcription and DNA-damage repair1,2. It hydrolyses ATP to remodel chromatin structure by sliding and evicting histone octamers3–8, creating DNA regions that become accessible to other essential factors. However, our mechanistic understanding of the remodelling activity is hindered by the lack of a high-resolution structure of complexes from this family. Here we report the cryo-electron microscopy structure of Saccharomyces cerevisiae SWI/SNF bound to a nucleosome, at near-atomic resolution. In the structure, the actin-related protein (Arp) module is sandwiched between the ATPase and the rest of the complex, with the Snf2 helicase-SANT associated (HSA) domain connecting all modules. The body contains an assembly scaffold composed of conserved subunits Snf12 (also known as SMARCD or BAF60), Snf5 (also known as SMARCB1, BAF47 or INI1) and an asymmetric dimer of Swi3 (also known as SMARCC, BAF155 or BAF170). Another conserved subunit, Swi1 (also known as ARID1 or BAF250), resides in the core of SWI/SNF, acting as a molecular hub. We also observed interactions between Snf5 and the histones at the acidic patch, which could serve as an anchor during active DNA translocation. Our structure enables us to map and rationalize a subset of cancer-related mutations in the human SWI/SNF complex and to propose a model for how SWI/SNF recognizes and remodels the +1 nucleosome to generate nucleosome-depleted regions during gene activation9.

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Cryo-EM structure of SWI/SNF complex bound to a nucleosome

Abstract

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UN SDGs

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SWI/SNF nucleosome complex with ADP-BeFx

SWI/SNF Body Module

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Cryo-EM structure of SWI/SNF complex bound to a nucleosome

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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SWI/SNF nucleosome complex with ADP-BeFx

SWI/SNF Body Module

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