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Structural basis for histone H2B deubiquitination by the SAGA DUB module
Author(s) -
Morgan Michael Thomas,
HajYahya Mahmood,
Ringel Alison E.,
Bandi Prasanthi,
Brik Ashraf,
Wolberger Cynthia
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.803.14
Subject(s) - histone h2b , coactivator , ubiquitin , histone , microbiology and biotechnology , chemistry , biology , transcription factor , biochemistry , gene
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. 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. 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. Support or Funding Information Supported by grant GM‐095822 from the National Institute of General Medical Sciences (C.W.) and by a Ruth L. Kirschstein National Research Service Award (M.M.). A. Brik is a Neubauer Professor. GM/CA @ APS has been funded by the National Cancer Institute (Y1‐CO‐1020) and the National Institute of General Medical Sciences (Y1‐GM‐1104).