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

Mol Endocrinol. 2010 Jun;24(6):1165-74. doi: 10.1210/me.2009-0421. Epub 2010 Mar 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androgens / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chromatin Assembly and Disassembly / drug effects*
  • Chromatin Assembly and Disassembly / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / 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
  • Serine Endopeptidases / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic / drug effects*


  • AR protein, human
  • Androgens
  • CHD8 protein, human
  • DNA-Binding Proteins
  • Receptors, Androgen
  • Transcription Factors
  • Serine Endopeptidases
  • TMPRSS2 protein, human