PARP-1 Controls the Adipogenic Transcriptional Program by PARylating C/EBPβ and Modulating Its Transcriptional Activity

Xin Luo, Keun Woo Ryu, Dae Seok Kim, Tulip Nandu, Carlos J. Medina, Rebecca Gupte, Bryan A. Gibson, Raymond E. Soccio, Yonghao Yu, Rana K Gupta, William L Kraus

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)260-271
Number of pages12
JournalMolecular Cell
Volume65
Issue number2
DOIs
StatePublished - Jan 19 2017

Fingerprint

Adenosine Diphosphate
Poly C
Adipogenesis
Post Translational Protein Processing
Transcription Factors
Amino Acids
Mutation
DNA
Genes

Keywords

  • adipogenesis
  • C/EBPβ
  • DNA binding
  • gene expression
  • PARP inhibitor
  • PARP-1
  • PARylation
  • poly(ADP-ribose)
  • transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

PARP-1 Controls the Adipogenic Transcriptional Program by PARylating C/EBPβ and Modulating Its Transcriptional Activity. / Luo, Xin; Ryu, Keun Woo; Kim, Dae Seok; Nandu, Tulip; Medina, Carlos J.; Gupte, Rebecca; Gibson, Bryan A.; Soccio, Raymond E.; Yu, Yonghao; Gupta, Rana K; Kraus, William L.

In: Molecular Cell, Vol. 65, No. 2, 19.01.2017, p. 260-271.

Research output: Contribution to journalArticle

Luo, Xin ; Ryu, Keun Woo ; Kim, Dae Seok ; Nandu, Tulip ; Medina, Carlos J. ; Gupte, Rebecca ; Gibson, Bryan A. ; Soccio, Raymond E. ; Yu, Yonghao ; Gupta, Rana K ; Kraus, William L. / PARP-1 Controls the Adipogenic Transcriptional Program by PARylating C/EBPβ and Modulating Its Transcriptional Activity. In: Molecular Cell. 2017 ; Vol. 65, No. 2. pp. 260-271.
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