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

被引：89

作者：

Luo, Xin ^{[1
,2
,3
]}

Ryu, Keun Woo ^{[1
,2
,3
]}

Kim, Dae-Seok ^{[1
,2
]}

Nandu, Tulip ^{[1
,2
]}

Medina, Carlos J. ^{[4
]}

Gupte, Rebecca ^{[1
,2
]}

Gibson, Bryan A. ^{[1
,2
,5
]}

Soccio, Raymond E. ^{[4
]}

Yu, Yonghao ^{[6
]}

Gupta, Rana K. ^{[7
]}

Kraus, W. Lee ^{[1
,2
,3
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Cecil H & Ida Green Ctr Reprod Biol Sci, Lab Signaling & Gene Regulat, Dallas, TX 75390 USA

[2] Univ Texas Southwestern Med Ctr Dallas, Dept Obstet & Gynecol, Div Basic Res, Dallas, TX 75390 USA

[3] Univ Texas Southwestern Med Ctr Dallas, Grad Sch Biomed Sci, Program Genet Dev & Dis, Dallas, TX 75390 USA

[4] Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA

[5] Univ Texas Southwestern Med Ctr Dallas, Grad Sch Biomed Sci, Program Mol Biophys, Dallas, TX 75390 USA

[6] Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

[7] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA

来源：

MOLECULAR CELL | 2017年 / 65卷 / 02期

基金：

美国国家卫生研究院;

关键词：

GENE-EXPRESSION; POLY(ADP-RIBOSE) POLYMERASES; 3T3-L1; PREADIPOCYTES; CHROMATIN-STRUCTURE; ADIPOCYTE FUNCTION; REGULATORY DOMAIN; ADP-RIBOSYLATION; GENOMIC ANALYSES; BINDING; DIFFERENTIATION;

D O I：

10.1016/j.molcel.2016.11.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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/EBP beta, 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/EBP beta's DNA binding and transcriptional activities and attenuates adipogenesis in various genetic and cell-basedmodels. Interestingly, PARP-1 catalytic activity drops precipitously during the first 48 hr of differentiation, corresponding to a release of C/EBP beta from PARylation-mediated inhibition. This promotes the binding of C/EBPb 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/EBP beta, enhances these early adipogenic events. Collectively, our results provide a clear example of how site-specific PARylation drives biological outcomes.

引用

页码：260 / 271

页数：12

共 44 条

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