Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis.
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.
Duke Scholars
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- RNA, Small Nucleolar
- Poly (ADP-Ribose) Polymerase-1
- Phosphorylation
- Mice
- Histones
- Gene Expression Regulation, Developmental
- Developmental Biology
- DNA Damage
- Cell Line
- Animals
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- RNA, Small Nucleolar
- Poly (ADP-Ribose) Polymerase-1
- Phosphorylation
- Mice
- Histones
- Gene Expression Regulation, Developmental
- Developmental Biology
- DNA Damage
- Cell Line
- Animals