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PMID: 20308527 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

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

Molecular endocrinology (Baltimore, Md.) ·Vol. 24 ·No. 6 ·2010-06-00 ·Pages 1165-74

Menon T, Yates JA, Bochar DA

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.

MeSH Terms
Androgens/pharmacology Cell Line, Tumor Cell Proliferation/drug effects Chromatin Assembly and Disassembly/drug effects,genetics DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation, Neoplastic/drug effects Humans Male Protein Binding/drug effects Protein Transport/drug effects Receptors, Androgen/metabolism Response Elements/genetics Serine Endopeptidases/genetics,metabolism Transcription Factors/genetics,metabolism Transcription, Genetic/drug effects
Chemicals
AR protein, human Androgens CHD8 protein, human DNA-Binding Proteins Receptors, Androgen Transcription Factors Serine Endopeptidases TMPRSS2 protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Menon Tushar
The Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109-0606, USA.
Yates Joel A
Bochar Daniel A
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Article Info
Journal
Molecular endocrinology (Baltimore, Md.)
Abbr.
Mol Endocrinol
ISSN
1944-9917
DOI
10.1210/me.2009-0421
Published
2010-06-00
Epub
2010-00-22
Pages
1165-74
Language
English
Region
United States
NLM ID
8801431
PMCID
PMC2875808
Subset
IM
Grants
NCI NIH HHS · P30 CA046592 · United States
NCI NIH HHS · 5 P30 CA46592 · United States
External Links
PubMed source DOI: 10.1210/me.2009-0421 PMC Full Text
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