Androgen-induced recruitment of RNA polymerase II to a nuclear receptor-p160 coactivator complex.
The androgen receptor, like other nuclear receptors, activates target genes by binding to hormone-responsive enhancers. Here we demonstrate that androgen induces robust recruitment of androgen receptor, members of the p160 coactivator family, and CREB-binding protein p300 specifically at the distant enhancer of prostate-specific antigen (PSA) gene. Unexpectedly, we found that RNA polymerase II (Pol II) is directly recruited to the enhancer in a hormone-dependent manner, independent of the proximal promoter, and that the isolated PSA enhancer can mediate efficient androgen induction of transcription. Inhibition of the Pol II carboxyl-terminal domain kinase activity with low concentrations of flavopiridol blocks Pol II transfer from the enhancer to the promoter and selectively abolishes PSA induction by androgen. Moreover, elevated levels of the p160 coactivator ACTR/AIB1 increase both androgen-dependent and -independent PSA expression, by facilitating Pol II recruitment to the enhancer. These results support a model in which nuclear receptors and their coactivators mediate hormone induction by serving as a staging platform for Pol II recruitment.
Louie
Maggie C
MC
Department of Biological Chemistry, University of California at Davis Cancer Center/Basic Science, University of California at Davis, Sacramento, CA 95817, USA.
Yang
Hong Qiong
HQ
Ma
Ai-Hong
AH
Xu
Wei
W
Zou
June X
JX
Kung
Hsing-Jien
HJ
Chen
Hong-Wu
HW
D000256:Adenoviridae / Q000235:genetics; D000728:Androgens / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D000728:Androgens; D002843:Chromatin; D009687:Nuclear Proteins; D015534:Trans-Activators; D008156:Luciferases; D012319:RNA Polymerase II