PARP-1 Controls the Adipogenic Transcriptional Program by PARylating C/EBPβ and Modulating Its Transcriptional Activity.
Journal Article (Journal Article)
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/EBPβ, 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/EBPβ'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/EBPβ from PARylation-mediated inhibition. This promotes the binding of C/EBPβ 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/EBPβ, enhances these early adipogenic events. Collectively, our results provide a clear example of how site-specific PARylation drives biological outcomes.
Full Text
Duke Authors
Cited Authors
- Luo, X; Ryu, KW; Kim, D-S; Nandu, T; Medina, CJ; Gupte, R; Gibson, BA; Soccio, RE; Yu, Y; Gupta, RK; Kraus, WL
Published Date
- January 19, 2017
Published In
Volume / Issue
- 65 / 2
Start / End Page
- 260 - 271
PubMed ID
- 28107648
Pubmed Central ID
- PMC5258183
Electronic International Standard Serial Number (EISSN)
- 1097-4164
Digital Object Identifier (DOI)
- 10.1016/j.molcel.2016.11.015
Language
- eng
Conference Location
- United States