O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence

Jong Sun Lee, Zhiguo Zhang

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. How HIRA-mediated nucleosome assembly of H3.3-H4 is regulated remains not well understood. Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. Taken together, these results support a model in which OGT modifies HIRA to regulate HIRA-H3.3 complex formation and H3.3 nucleosome assembly and reveal the mechanism by which OGT functions in cellular senescence.

Original languageEnglish (US)
Pages (from-to)E3213-E3220
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number23
DOIs
StatePublished - Jun 7 2016

Keywords

  • Cellular senescence
  • HIRA
  • Histone H3.3
  • Nucleosome assembly
  • OGT

ASJC Scopus subject areas

  • General

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