Transcriptional regulation of the androgen receptor cofactor androgen receptor trapped clone-27

Jerome C. Nwachukwu, Wenhui Li, Inés Pineda-Torra, Ying Huang Hong, Rachel Ruoff, Ellen Shapiro, Samir S. Taneja, Susan K. Logan, Michael J. Garabedian

    Research output: Contribution to journalArticle

    Abstract

    Cofactors modulate nuclear receptor activity and impact human health and disease, yet surprisingly little is known about their transcriptional regulation. Androgen receptor trapped clone-27 (ART-27) is a cofactor that binds to androgen receptor (AR) amino terminus and modulates AR-dependent transcription. Interestingly, ART-27 displays both a cell type- and developmental stage-specific expression pattern. However, the cis-acting elements and trans-acting factors affecting ART-27 gene expression have not been elucidated. We found that ART-27 gene expression is repressed and its promoter is histone H3-K27 tri-methylated in human embryonic kidney cells, but not prostate cells, and the histone deacetylase inhibitor, trichostatin A, relieves this inhibition. The DNA response elements that control the induction of ART-27 gene expression were also characterized. The major cis-acting element corresponds to a consensus cAMP-responsive element (CRE) and binds the CRE-binding protein (CREB) as shown by EMSA and chromatin immunoprecipitation assays. Furthermore, ART-27 promoter activity is induced upon CREB overexpression. Epidermal growth factor, which activates CREB via phosphorylation, also induces ART-27 expression, whereas a reduction in CREB phosphorylation or expression blocks this induction in prostate cells. In human prostate development, both epithelial and stromal cells express CREB; however, active phosphorylated CREB is restricted to epithelial cells where ART-27 is expressed. Based on these findings, we propose a transcriptional regulatory circuit for the developmental expression of ART-27 that includes repression by chromatin modification through a trichostatin A-sensitive factor and activation upon growth factor stimulation via CREB.

    Original languageEnglish (US)
    Pages (from-to)2864-2876
    Number of pages13
    JournalMolecular Endocrinology
    Volume21
    Issue number12
    DOIs
    StatePublished - Dec 1 2007

      Fingerprint

    ASJC Scopus subject areas

    • Molecular Biology
    • Endocrinology

    Cite this

    Nwachukwu, J. C., Li, W., Pineda-Torra, I., Hong, Y. H., Ruoff, R., Shapiro, E., Taneja, S. S., Logan, S. K., & Garabedian, M. J. (2007). Transcriptional regulation of the androgen receptor cofactor androgen receptor trapped clone-27. Molecular Endocrinology, 21(12), 2864-2876. https://doi.org/10.1210/me.2007-0094