Androgen-induced recruitment of RNA polymerase II to a nuclear receptor–p160 coactivator complex
| Autor: | Maggie C. Louie, Hongwu Chen, Hong Qiong Yang, Wei Xu, June X. Zou, Hsing Jien Kung, Ai Hong Ma |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Transcription
Genetic medicine.drug_class Genetic Vectors RNA polymerase II Enhancer RNAs Biology urologic and male genital diseases Transfection Models Biological Adenoviridae Transcription (biology) Genes Reporter Coactivator medicine Tumor Cells Cultured Humans Enhancer Luciferases Promoter Regions Genetic Cell Nucleus Multidisciplinary Nuclear Proteins Biological Sciences Androgen Molecular biology Precipitin Tests Chromatin Protein Structure Tertiary Androgen receptor Enhancer Elements Genetic Nuclear receptor biology.protein Androgens Trans-Activators RNA Polymerase II Protein Binding |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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