Regulation of Androgen-Responsive Transcription by the Chromatin Remodeling Factor CHD8
Regulation of Androgen-Responsive Transcription by the Chromatin Remodeling Factor CHD8
The androgen receptor (AR) mediates the effect of androgens through its transcriptional function during both normal prostate development and in the emergence and progression of prostate cancer. AR is known to assemble coactivator complexes at target promoters to facilitate transcriptional activation in response to androgens. Here we identify the ATP-dependent chromatin remodeling factor chromodomain helicase DNA-binding protein 8 (CHD8) as a novel coregulator of androgen-responsive transcription. We demonstrate that CHD8 directly associates with AR and that CHD8 and AR simultaneously localize to the TMPRSS2 enhancer after androgen treatment. In the LNCaP cell line, reduction of CHD8 levels by small interfering RNA treatment severely diminishes androgen-dependent activation of the TMPRSS2 gene. We demonstrate that the recruitment of AR to the TMPRSS2 promoter in response to androgen treatment requires CHD8. Finally, CHD8 facilitates androgen-stimulated proliferation of LNCaP cells, emphasizing the physiological importance of CHD8. Taken together, we present evidence of a functional role for CHD8 in AR-mediated transcriptional regulation of target genes.
- University of Michigan–Ann Arbor United States
- University of Michigan–Flint United States
Male, Transcription, Genetic, Serine Endopeptidases, Chromatin Assembly and Disassembly, Response Elements, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Protein Transport, Receptors, Androgen, Cell Line, Tumor, Androgens, Humans, Cell Proliferation, Protein Binding, Transcription Factors
Male, Transcription, Genetic, Serine Endopeptidases, Chromatin Assembly and Disassembly, Response Elements, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Protein Transport, Receptors, Androgen, Cell Line, Tumor, Androgens, Humans, Cell Proliferation, Protein Binding, Transcription Factors
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