| First Author | Luo X | Year | 2017 |
| Journal | Mol Cell | Volume | 65 |
| Issue | 2 | Pages | 260-271 |
| PubMed ID | 28107648 | Mgi Jnum | J:240603 |
| Mgi Id | MGI:5888790 | Doi | 10.1016/j.molcel.2016.11.015 |
| Citation | Luo X, et al. (2017) PARP-1 Controls the Adipogenic Transcriptional Program by PARylating C/EBPbeta and Modulating Its Transcriptional Activity. Mol Cell 65(2):260-271 |
| abstractText | Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins mediated by PARP family members, such as PARP-1. Although PARylation has been studied extensively, few examples of definitive biological roles for site-specific PARylation have been reported. Here we show that C/EBPbeta, a key pro-adipogenic transcription factor, is PARylated by PARP-1 on three amino acids in a conserved regulatory domain. PARylation at these sites inhibits C/EBPbeta's DNA binding and transcriptional activities and attenuates adipogenesis in various genetic and cell-based models. Interestingly, PARP-1 catalytic activity drops precipitously during the first 48 hr of differentiation, corresponding to a release of C/EBPbeta from PARylation-mediated inhibition. This promotes the binding of C/EBPbeta at enhancers controlling the expression of adipogenic target genes and continued differentiation. Depletion or chemical inhibition of PARP-1, or mutation of the PARylation sites on C/EBPbeta, enhances these early adipogenic events. Collectively, our results provide a clear example of how site-specific PARylation drives biological outcomes. |
