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