title: Poly(ADP-ribose) polymerase 1 is a key regulator of estrogen receptor α-dependent gene transcription.
abstract: Activation of nuclear receptor estrogen receptor α (ERα) exerts cardiovascular protective effects by modulating the expression of ERα target genes. However, the underlying mechanism remains unclear. PARP1 is a ubiquitous multifunctional nuclear enzyme. In this study, we examined the interplay between PARP1 and ERα, and identified PARP1 as an important regulator of ERα-dependent transcription. We showed that PARP1 could directly bind to ERα, and ERα could be poly(ADP-ribosyl)ated by PARP1. Poly(ADP-ribosyl)ation increased ERα binding to estrogen response element (ERE) present in the promoter of target genes and promoted ERα-mediated gene transcription. Estradiol, the ligand of ERα, increased PARP enzymatic activity and enhanced poly(ADP-ribosyl)ation of ERα. Upon treatment with estradiol, ERα binding to ERE- and ERα-dependent gene expression was dramatically increased in cultured vascular smooth muscle cells (VSMCs). Inhibition of PARP1 by PARP inhibitor or PARP1 siRNA decreased ERα binding to ERE and prevented ERα-dependent gene transcription in VSMCs. Further studies revealed that PARP1 served as an indispensible component for the formation of the ERα-ERE complex by directly interacting with ERα. Thus, our results identify PARP1 as a key regulator of ERα in controlling ERα transactivation.
authors.affiliation: Department of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Wuhan, China 430022.
authors.forename: Fengxiao
authors.initials: F
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Luo
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Du
authors.forename: Fangmei
authors.initials: F
authors.lastname: Liu
authors.forename: Ting
authors.initials: T
authors.lastname: Luo
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020218:Response Elements / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases