Modulation of the expression and transactivation of androgen receptor by the basic helix-loop-helix transcription factor Pod-1 through recruitment of histone deacetylase 1.
Androgen receptor (AR) is important in male sexual differentiation and testicular function. Here, we demonstrate the regulation of AR expression and its transactivation by the basic helix-loop-helix (bHLH) transcription factor Pod-1, the expression of which in postnatal testis reciprocally coincides with the expression of AR. Pod-1 represses the promoter activity of AR, possibly through its E-box. An AR promoter region of 169 bp, which harbors one canonical E-box, is sufficient for the Pod-1-repression and bound by purified Pod-1 proteins. Pod-1 also suppresses the transactivation of AR. Transient transfection analyses of mammalian cells show that Pod-1 represses AR transactivation in a dose-dependent manner. Furthermore, yeast two-hybrid, glutathione-S-transferase-pull-down, and co-immunoprecipitation analyses reveal that Pod-1 directly associates with AR through its N-terminal region and through the DNA binding-hinge domain of AR. Interestingly, Pod-1 recruits histone deacetylase (HDAC)-1 to inhibit both promoter activity and transactivation of AR. Overexpression of HDAC1 further inhibits the Pod-1-mediated repressions and Pod-1 directly interacts with HDAC1. Furthermore, chromatin immunoprecipitation assay reveals that HDAC1 is recruited with Pod-1 to the endogenous AR promoter and the androgen-regulated Pem promoter. Taken together, these results suggest that Pod-1, which controls AR transcription and function, may play an important role in the development and function of the testis.
Hong
Cheol Yi
CY
Hormone Research Center, School of Biological Sciences and Research, Chonnam National University, Gwangju 500-757, Republic of Korea.
Gong
Eun-Yeung
EY
Kim
Kabsun
K
Suh
Ji Ho
JH
Ko
Hyun-Mi
HM
Lee
Hyun Joo
HJ
Choi
Hueng-Sik
HS
Lee
Keesook
K
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D024721:E-Box Elements; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D013737:Testis / Q000254:growth & development; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
D051792:Basic Helix-Loop-Helix Proteins; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D018398:Homeodomain Proteins; D011944:Receptors, Androgen; D014157:Transcription Factors; C112923:Tcf21 protein, mouse; C484389:Hdac1 protein, mouse; C498048:Rhox5 protein, mouse