Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis

Dan Huang, Cristel V. Camacho, Rohit Setlem, Keun Woo Ryu, Balaji Parameswaran, Rana K. Gupta, W. Lee Kraus

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Although ADP-ribosylation of histones by PARP-1 has been linked to genotoxic stress responses, its role in physiological processes and gene expression has remained elusive. We found that NAD+-dependent ADP-ribosylation of histone H2B-Glu35 by small nucleolar RNA (snoRNA)-activated PARP-1 inhibits AMP kinase-mediated phosphorylation of adjacent H2B-Ser36, which is required for the proadipogenic gene expression program. The activity of PARP-1 on H2B requires NMNAT-1, a nuclear NAD+ synthase, which directs PARP-1 catalytic activity to Glu and Asp residues. ADP-ribosylation of Glu35 and the subsequent reduction of H2B-Ser36 phosphorylation inhibits the differentiation of adipocyte precursors in cultured cells. Parp1 knockout in preadipocytes in a mouse lineage-tracing genetic model increases adipogenesis, leading to obesity. Collectively, our results demonstrate a functional interplay between H2B-Glu35 ADP-ribosylation and H2B-Ser36 phosphorylation that controls adipogenesis.

Original languageEnglish (US)
Pages (from-to)934-949.e14
JournalMolecular cell
Issue number6
StatePublished - Sep 17 2020


  • ADP-ribosylation
  • PARP-1
  • adipogenesis
  • differentiation
  • histones
  • phosphorylation
  • proliferation
  • proteomics
  • snoRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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