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

Authors
  • Menon, Tushar
  • Yates, Joel A
  • Bochar, Daniel A
Type
Published Article
Journal
Molecular Endocrinology
Publisher
The Endocrine Society
Publication Date
Jun 01, 2010
Volume
24
Issue
6
Pages
1165–1174
Identifiers
DOI: 10.1210/me.2009-0421
PMID: 20308527
Source
Medline
License
Unknown

Abstract

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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