2. Academic Validation
  3. SENP3 and USP7 regulate Polycomb-rixosome interactions and silencing functions

SENP3 and USP7 regulate Polycomb-rixosome interactions and silencing functions

  • Cell Rep. 2023 Apr 3;42(4):112339. doi: 10.1016/j.celrep.2023.112339.
Haining Zhou 1,  Wenzhi Feng 2,  Juntao Yu 2,  Tiasha A Shafiq 2,  Joao A Paulo 3,  Jiuchun Zhang 4,  Zhenhua Luo 5,  Steven P Gygi 3,  Danesh Moazed 6
Affiliations

Affiliations

  • 1 Howard Hughes Medical Institute, Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: zhouhaining@ibp.ac.cn.
  • 2 Howard Hughes Medical Institute, Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  • 3 Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  • 4 Initiative for Genome Editing and Neurodegeneration, Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  • 5 Precision Medicine Institute, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 6 Howard Hughes Medical Institute, Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. Electronic address: danesh@hms.harvard.edu.
PMID: 37014752 DOI: 10.1016/j.celrep.2023.112339
Abstract

The rixosome and PRC1 silencing complexes are associated with deSUMOylating and deubiquitinating Enzymes, SENP3 and USP7, respectively. How deSUMOylation and deubiquitylation contribute to rixosome- and Polycomb-mediated silencing is not fully understood. Here, we show that the enzymatic activities of SENP3 and USP7 are required for silencing of Polycomb target genes. SENP3 deSUMOylates several rixosome subunits, and this activity is required for association of the rixosome with PRC1. USP7 associates with canonical PRC1 (cPRC1) and deubiquitinates the chromodomain subunits CBX2 and CBX4, and inhibition of USP activity results in disassembly of cPRC1. Finally, both SENP3 and USP7 are required for Polycomb- and rixosome-dependent silencing at an ectopic reporter locus. These findings demonstrate that SUMOylation and ubiquitination regulate the assembly and activities of the rixosome and Polycomb complexes and raise the possibility that these modifications provide regulatory mechanisms that may be utilized during development or in response to environmental challenges.

Keywords

CP: Molecular biology; SENP3; SUMO; USP7; deSUMOylation; deubiquitination; epigenetics; gene silencing; heterochromatin; polycomb; rixosome; ubiquitin.

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