| First Author | Huang D | Year | 2020 |
| Journal | Mol Cell | Volume | 79 |
| Issue | 6 | Pages | 934-949.e14 |
| PubMed ID | 32822587 | Mgi Jnum | J:297184 |
| Mgi Id | MGI:6468977 | Doi | 10.1016/j.molcel.2020.08.002 |
| Citation | Huang D, et al. (2020) Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis. Mol Cell 79(6):934-949.e14 |
| abstractText | 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. |
