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Publication : Regulation of androgen-responsive transcription by the chromatin remodeling factor CHD8.

First Author  Menon T Year  2010
Journal  Mol Endocrinol Volume  24
Issue  6 Pages  1165-74
PubMed ID  20308527 Mgi Jnum  J:162265
Mgi Id  MGI:4818530 Doi  10.1210/me.2009-0421
Citation  Menon T, et al. (2010) Regulation of androgen-responsive transcription by the chromatin remodeling factor CHD8. Mol Endocrinol 24(6):1165-74
abstractText  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.
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