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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

Hormone Research Center, School of Biological Sciences and Technology (C.Y.H., E.-Y.G., K.K., J.H.S., H.J.L., H.-S.C., K.L.), and Department of Biological Sciences (H.-M.K.), Chonnam National University, Gwangju 500-757, Republic of Korea

Address all correspondence and requests for reprints to: Keesook Lee, Hormone Research Center, Chonnam National University, Gwangju 500-757, Republic of Korea. E-mail: klee{at}chonnam.ac.kr.

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 coimmunoprecipitation 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.

NURSA Molecule Pages Link:

Nuclear Receptors:   AR

Coregulators:   Pod-1  |  HDAC4  |  HDAC1

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