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Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2226-30. Epub 2003 Feb 14.

Androgen-induced recruitment of RNA polymerase II to a nuclear receptor-p160 coactivator complex.

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  • 1Department of Biological Chemistry, University of California at Davis Cancer Center/Basic Science, University of California at Davis, Sacramento, CA 95817, USA.

Abstract

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.

PMID:
12589022
[PubMed - indexed for MEDLINE]
PMCID:
PMC151322
Free PMC Article

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