skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Structural basis for histone H2B deubiquitination by the SAGA DUB module

Abstract

Monoubiquitinated histone H2B plays multiple roles in transcription activation. H2B is deubiquitinated by the Spt-Ada-Gcn5 acetyltransferase (SAGA) coactivator, which contains a four-protein subcomplex known as the deubiquitinating (DUB) module. In this paper, the crystal structure of the Ubp8/Sgf11/Sus1/Sgf73 DUB module bound to a ubiquitinated nucleosome reveals that the DUB module primarily contacts H2A/H2B, with an arginine cluster on the Sgf11 zinc finger domain docking on the conserved H2A/H2B acidic patch. The Ubp8 catalytic domain mediates additional contacts with H2B, as well as with the conjugated ubiquitin. Finally, we find that the DUB module deubiquitinates H2B both in the context of the nucleosome and in H2A/H2B dimers complexed with the histone chaperone, FACT, suggesting that SAGA could target H2B at multiple stages of nucleosome disassembly and reassembly during transcription.

Authors:
 [1];  [2];  [1];  [1];  [3];  [1]
  1. Johns Hopkins Univ., Baltimore, MD (United States). School of Medicine. Dept. of Biophysics and Biophysical Chemistry
  2. Ben-Gurion Univ. of the Negev, Beer Sheva (Israel). Dept. of Chemistry
  3. Technion-Israel Inst. of Technology, Haifa (Israel). Schulich Faculty of Chemistry
Publication Date:
Research Org.:
Johns Hopkins Univ., Baltimore, MD (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States)
Contributing Org.:
Ben-Gurion Univ. of the Negev, Beer Sheva (Israel); Technion-Israel Inst. of Technology, Haifa (Israel)
OSTI Identifier:
1249222
Grant/Contract Number:  
AC02-06CH11357; GM-095822; Y1-CO-1020; Y1-GM-1104
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Science
Additional Journal Information:
Journal Volume: 351; Journal Issue: 6274; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Morgan, Michael T., Haj-Yahya, Mahmood, Ringel, Alison E., Bandi, Prasanthi, Brik, Ashraf, and Wolberger, Cynthia. Structural basis for histone H2B deubiquitination by the SAGA DUB module. United States: N. p., 2016. Web. doi:10.1126/science.aac5681.
Morgan, Michael T., Haj-Yahya, Mahmood, Ringel, Alison E., Bandi, Prasanthi, Brik, Ashraf, & Wolberger, Cynthia. Structural basis for histone H2B deubiquitination by the SAGA DUB module. United States. https://doi.org/10.1126/science.aac5681
Morgan, Michael T., Haj-Yahya, Mahmood, Ringel, Alison E., Bandi, Prasanthi, Brik, Ashraf, and Wolberger, Cynthia. 2016. "Structural basis for histone H2B deubiquitination by the SAGA DUB module". United States. https://doi.org/10.1126/science.aac5681. https://www.osti.gov/servlets/purl/1249222.
@article{osti_1249222,
title = {Structural basis for histone H2B deubiquitination by the SAGA DUB module},
author = {Morgan, Michael T. and Haj-Yahya, Mahmood and Ringel, Alison E. and Bandi, Prasanthi and Brik, Ashraf and Wolberger, Cynthia},
abstractNote = {Monoubiquitinated histone H2B plays multiple roles in transcription activation. H2B is deubiquitinated by the Spt-Ada-Gcn5 acetyltransferase (SAGA) coactivator, which contains a four-protein subcomplex known as the deubiquitinating (DUB) module. In this paper, the crystal structure of the Ubp8/Sgf11/Sus1/Sgf73 DUB module bound to a ubiquitinated nucleosome reveals that the DUB module primarily contacts H2A/H2B, with an arginine cluster on the Sgf11 zinc finger domain docking on the conserved H2A/H2B acidic patch. The Ubp8 catalytic domain mediates additional contacts with H2B, as well as with the conjugated ubiquitin. Finally, we find that the DUB module deubiquitinates H2B both in the context of the nucleosome and in H2A/H2B dimers complexed with the histone chaperone, FACT, suggesting that SAGA could target H2B at multiple stages of nucleosome disassembly and reassembly during transcription.},
doi = {10.1126/science.aac5681},
url = {https://www.osti.gov/biblio/1249222}, journal = {Science},
issn = {0036-8075},
number = 6274,
volume = 351,
place = {United States},
year = {Fri Feb 12 00:00:00 EST 2016},
month = {Fri Feb 12 00:00:00 EST 2016}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 177 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Combinatorial depletion analysis to assemble the network architecture of the SAGA and ADA chromatin remodeling complexes
journal, January 2011


Chromatin Protocols
book, January 1999


Chromatin Protocols
journal, February 2001


Highly Efficient and Chemoselective Peptide Ubiquitylation
journal, October 2009


Structural basis of histone H2A–H2B recognition by the essential chaperone FACT
journal, May 2013


The Deubiquitylation Activity of Ubp8 Is Dependent upon Sgf11 and Its Association with the SAGA Complex
journal, January 2005


Uncovering the Role of Sgf73 in Maintaining SAGA Deubiquitinating Module Structure and Activity
journal, April 2015


H2B Ubiquitylation Plays a Role in Nucleosome Dynamics during Transcription Elongation
journal, July 2008


Expeditious Chemical Synthesis of Ubiquitinated Peptides Employing Orthogonal Protection and Native Chemical Ligation
journal, February 2011


Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast
journal, June 2002


FACT Facilitates Transcription-Dependent Nucleosome Alteration
journal, August 2003


Tyrosine phosphorylation of histone H2A by CK2 regulates transcriptional elongation
journal, September 2014


Chromatin Protocols
book, January 2015


XDS
journal, January 2010


ATAC-king the complexity of SAGA during evolution
journal, March 2012


Bre1, an E3 Ubiquitin Ligase Required for Recruitment and Substrate Selection of Rad6 at a Promoter
journal, January 2003


Crystal Structures of Nucleosome Core Particles Containing the ‘601’ Strong Positioning Sequence
journal, October 2010


Mapping the Deubiquitination Module within the SAGA Complex
journal, November 2014


Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography
journal, July 2013


PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010


Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation
journal, April 2008


DNA Binding by Sgf11 Protein Affects Histone H2B Deubiquitination by Spt-Ada-Gcn5-Acetyltransferase (SAGA)
journal, February 2014


FACT Disrupts Nucleosome Structure by Binding H2A-H2B with Conserved Peptide Motifs
journal, October 2015


Histone H2B ubiquitination: signaling not scrapping
journal, June 2014


A Conserved Mechanism for Centromeric Nucleosome Recognition by Centromere Protein CENP-C
journal, May 2013


Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome
journal, October 2014


A Role for Intersubunit Interactions in Maintaining SAGA Deubiquitinating Module Structure and Activity
journal, August 2012


Highly Efficient and Chemoselective Peptide Ubiquitylation
journal, October 2009


Scaling and assessment of data quality
journal, December 2005


Squeezing the most from every crystal: the fine details of data collection
journal, June 2013


Structure of RCC1 chromatin factor bound to the nucleosome core particle
journal, August 2010


Structural Basis of Silencing: Sir3 BAH Domain in Complex with a Nucleosome at 3.0 A Resolution
journal, November 2011


The Nucleosome Acidic Patch Regulates the H2B K123 Monoubiquitylation Cascade and Transcription Elongation in Saccharomyces cerevisiae
journal, August 2015


New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning
journal, February 1998


Synthesis of proteins by native chemical ligation
journal, November 1994


Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021


Role of the Ada2 and Ada3 Transcriptional Coactivators in Histone Acetylation
journal, December 2001


Architecture of the S accharomyces cerevisiae SAGA transcription coactivator complex
journal, September 2014


Yeast Ataxin-7 links histone deubiquitination with gene gating and mRNA export
journal, May 2008


Structural Insights into the Assembly and Function of the SAGA Deubiquitinating Module
journal, April 2010


Phaser crystallographic software
journal, July 2007


Writing and reading H2B monoubiquitylation
journal, August 2014


PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010


Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome
text, January 2014


Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation
text, January 2008


Works referencing / citing this record:

Structure of H3K36-methylated nucleosome–PWWP complex reveals multivalent cross-gyre binding
journal, December 2019


Bulky Histone Modifications May Have an Oversized Role in Nucleosome Dynamics
journal, November 2019


The RNF168 paralog RNF169 defines a new class of ubiquitylated histone reader involved in the response to DNA damage.
text, January 2017


The nucleosome acidic patch directly interacts with subunits of the Paf1 and FACT complexes and controls chromatin architecture in vivo
journal, June 2019


Structure of ubiquitylated-Rpn10 provides insight into its autoregulation mechanism
journal, October 2016


Nucleosome structure and dynamics are coming of age
journal, December 2018


FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics
posted_content, August 2018


Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome
journal, August 2018


Breaking the chains: deubiquitylating enzyme specificity begets function
journal, February 2019


FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics
journal, January 2019


Structure of the transcription coactivator SAGA
journal, January 2020


Architecture of Saccharomyces cerevisiae SAGA complex
journal, May 2019


Total chemical synthesis of SUMO-2-Lys63-linked diubiquitin hybrid chains assisted by removable solubilizing tags
journal, January 2017


The interplay of histone H2B ubiquitination with budding and fission yeast heterochromatin
journal, February 2018


A molecular engineering toolbox for the structural biologist
journal, January 2017


Thiirane linkers directed histone H2A diubiquitination suggests plasticity in 53BP1 recognition
journal, January 2019


Enhancing NMR derived ensembles with kinetics on multiple timescales
journal, December 2019


Structural mechanism for the recognition and ubiquitination of a single nucleosome residue by Rad6–Bre1
journal, September 2016


Role of remodeling and spacing factor 1 in histone H2A ubiquitination-mediated gene silencing
journal, August 2017


SAGA complex mediates the transcriptional up-regulation of antiviral RNA silencing
journal, April 2017


Nucleosome and ubiquitin position Set2 to methylate H3K36
journal, August 2019


A role for Mog1 in H2Bub1 and H3K4me3 regulation affecting RNAPII transcription and mRNA export
journal, September 2018


ISWI chromatin remodellers sense nucleosome modifications to determine substrate preference
journal, August 2017


Total chemical synthesis of histones and their analogs, assisted by native chemical ligation and palladium complexes
journal, October 2017


A basic motif anchoring ISWI to nucleosome acidic patch regulates nucleosome spacing
journal, December 2019


DNA damage detection in nucleosomes involves DNA register shifting
journal, May 2019


The structural basis of modified nucleosome recognition by 53BP1
journal, July 2016


Cryo-EM of nucleosome core particle interactions in trans
journal, May 2018


Structural basis of nucleosome recognition and modification by MLL methyltransferases
journal, September 2019


The Chd1 chromatin remodeler shifts hexasomes unidirectionally
journal, December 2016


Centromeres are maintained by fastening CENP-A to DNA and directing an arginine anchor-dependent nucleosome transition
journal, June 2017


Active site alanine mutations convert deubiquitinases into high‐affinity ubiquitin‐binding proteins
journal, August 2018


Structural diversity of the nucleosome
journal, November 2017


Structural Basis of H2B Ubiquitination-Dependent H3K4 Methylation by COMPASS
journal, December 2019


The Chd1 chromatin remodeler shifts hexasomes unidirectionally
journal, October 2016


The nucleosome acidic patch directly interacts with subunits of the Paf1 and FACT complexes and controls chromatin architecture in vivo
journal, May 2019


Architecture of Saccharomyces cerevisiae SAGA complex
journal, May 2019


Nucleosome and ubiquitin position Set2 to methylate H3K36
journal, August 2019


A systematic analysis of nucleosome core particle and nucleosome-nucleosome stacking structure
journal, January 2018


Cryo-EM of nucleosome core particle interactions in trans
journal, May 2018


An insight into structural plasticity and conformational transitions of transcriptional co-activator Sus1
journal, March 2020


Specificity for deubiquitination of monoubiquitinated FANCD2 is driven by the N-terminus of USP1
journal, October 2018


Total Chemical Synthesis of Modified Histones
journal, February 2018


The Histone Code of Senescence
journal, February 2020


FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics
journal, January 2019