TY - JOUR
T1 - Androgen-induced recruitment of RNA polymerase II to a nuclear receptor-p160 coactivator complex
AU - Louie, Maggie C.
AU - Yang, Hong Qiong
AU - Ma, Ai Hong
AU - Xu, Wei
AU - Zou, June X.
AU - Kung, Hsing Jien
AU - Chen, Hong Wu
PY - 2003/3/4
Y1 - 2003/3/4
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.0437824100
DO - 10.1073/pnas.0437824100
M3 - Article
C2 - 12589022
AN - SCOPUS:0037418280
SN - 0027-8424
VL - 100
SP - 2226
EP - 2230
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -