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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Huang, D; Camacho, CV; Setlem, R; Ryu, KW; Parameswaran, B; Gupta, RK; Kraus, WL

Published Date

  • September 17, 2020

Published In

Volume / Issue

  • 79 / 6

Start / End Page

  • 934 - 949.e14

PubMed ID

  • 32822587

Pubmed Central ID

  • PMC7502539

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2020.08.002

Language

  • eng

Conference Location

  • United States