Structural Basis for Histone H2B Deubiquitination by the SAGA DUB Module

Overview

Journal Science

Specialty Science

Date 2016 Feb 26

PMID 26912860

Citations 130

Authors

Michael T Morgan

Mahmood Haj-Yahya

Alison E Ringel

Prasanthi Bandi

Ashraf Brik

Cynthia Wolberger

Affiliations

Soon will be listed here.

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. 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.

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References

Formosa T, Eriksson P, Wittmeyer J, Ginn J, Yu Y, Stillman D . Spt16-Pob3 and the HMG protein Nhp6 combine to form the nucleosome-binding factor SPN. EMBO J. 2001; 20(13):3506-17. PMC: 125512. DOI: 10.1093/emboj/20.13.3506. View

Balasubramanian R, Pray-Grant M, Selleck W, Grant P, Tan S . Role of the Ada2 and Ada3 transcriptional coactivators in histone acetylation. J Biol Chem. 2002; 277(10):7989-95. DOI: 10.1074/jbc.M110849200. View

Sun Z, Allis C . Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature. 2002; 418(6893):104-8. DOI: 10.1038/nature00883. View

Wood A, Krogan N, Dover J, Schneider J, Heidt J, Boateng M . Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Mol Cell. 2003; 11(1):267-74. DOI: 10.1016/s1097-2765(02)00802-x. View

Belotserkovskaya R, Oh S, Bondarenko V, Orphanides G, Studitsky V, Reinberg D . FACT facilitates transcription-dependent nucleosome alteration. Science. 2003; 301(5636):1090-3. DOI: 10.1126/science.1085703. View

Henry K, Wyce A, Lo W, Duggan L, Emre N, Kao C . Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8. Genes Dev. 2003; 17(21):2648-63. PMC: 280615. DOI: 10.1101/gad.1144003. View

Barbera A, Chodaparambil J, Kelley-Clarke B, Joukov V, Walter J, Luger K . The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA. Science. 2006; 311(5762):856-61. DOI: 10.1126/science.1120541. View

Pavri R, Zhu B, Li G, Trojer P, Mandal S, Shilatifard A . Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell. 2006; 125(4):703-17. DOI: 10.1016/j.cell.2006.04.029. View

Zhang X, Varthi M, Sykes S, Phillips C, Warzecha C, Zhu W . The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Mol Cell. 2008; 29(1):102-11. PMC: 2254522. DOI: 10.1016/j.molcel.2007.12.015. View

10.

Kohler A, Schneider M, Cabal G, Nehrbass U, Hurt E . Yeast Ataxin-7 links histone deubiquitination with gene gating and mRNA export. Nat Cell Biol. 2008; 10(6):707-15. DOI: 10.1038/ncb1733. View

11.

McGinty R, Kim J, Chatterjee C, Roeder R, Muir T . Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation. Nature. 2008; 453(7196):812-6. PMC: 3774535. DOI: 10.1038/nature06906. View

12.

Fleming A, Kao C, Hillyer C, Pikaart M, Osley M . H2B ubiquitylation plays a role in nucleosome dynamics during transcription elongation. Mol Cell. 2008; 31(1):57-66. DOI: 10.1016/j.molcel.2008.04.025. View

13.

Kohler A, Zimmerman E, Schneider M, Hurt E, Zheng N . Structural basis for assembly and activation of the heterotetrameric SAGA histone H2B deubiquitinase module. Cell. 2010; 141(4):606-17. PMC: 2901531. DOI: 10.1016/j.cell.2010.04.026. View

14.

Samara N, Datta A, Berndsen C, Zhang X, Yao T, Cohen R . Structural insights into the assembly and function of the SAGA deubiquitinating module. Science. 2010; 328(5981):1025-9. PMC: 4220450. DOI: 10.1126/science.1190049. View

15.

Makde R, England J, Yennawar H, Tan S . Structure of RCC1 chromatin factor bound to the nucleosome core particle. Nature. 2010; 467(7315):562-6. PMC: 3168546. DOI: 10.1038/nature09321. View

16.

Vasudevan D, Chua E, Davey C . Crystal structures of nucleosome core particles containing the '601' strong positioning sequence. J Mol Biol. 2010; 403(1):1-10. DOI: 10.1016/j.jmb.2010.08.039. View

17.

Lee K, Sardiu M, Swanson S, Gilmore J, Torok M, Grant P . Combinatorial depletion analysis to assemble the network architecture of the SAGA and ADA chromatin remodeling complexes. Mol Syst Biol. 2011; 7:503. PMC: 3159981. DOI: 10.1038/msb.2011.40. View

18.

Armache K, Garlick J, Canzio D, Narlikar G, Kingston R . Structural basis of silencing: Sir3 BAH domain in complex with a nucleosome at 3.0 Å resolution. Science. 2011; 334(6058):977-82. PMC: 4098850. DOI: 10.1126/science.1210915. View

19.

Spedale G, Timmers H, Pijnappel W . ATAC-king the complexity of SAGA during evolution. Genes Dev. 2012; 26(6):527-41. PMC: 3315114. DOI: 10.1101/gad.184705.111. View

20.

Samara N, Ringel A, Wolberger C . A role for intersubunit interactions in maintaining SAGA deubiquitinating module structure and activity. Structure. 2012; 20(8):1414-24. PMC: 3423971. DOI: 10.1016/j.str.2012.05.015. View