title: 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.
abstract: 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.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Research, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Cheol Yi
authors.initials: CY
authors.lastname: Hong
authors.forename: Eun-Yeung
authors.initials: EY
authors.lastname: Gong
authors.forename: Kabsun
authors.initials: K
authors.lastname: Kim
authors.forename: Ji Ho
authors.initials: JH
authors.lastname: Suh
authors.forename: Hyun-Mi
authors.initials: HM
authors.lastname: Ko
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hueng-Sik
authors.initials: HS
authors.lastname: Choi
authors.forename: Keesook
authors.initials: K
authors.lastname: Lee
mesh_terms: 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
chemical_list: 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