Repression of gonadotropin-releasing hormone promoter activity by the POU homeodomain transcription factor SCIP/Oct-6/Tst-1: A regulatory mechanism of phenotype expression?

Margaret E. Wierman, Xiaoyan Xiong, Jadwiga K. Kepa, Andrea J. Spaulding, Britta M. Jacobsen, Zhaoqin Fang, Gajanan Nilaver, Sergio R. Ojeda

    Research output: Contribution to journalArticle

    43 Scopus citations

    Abstract

    POU domain transcription factors are required for neuropeptide expression in selected subsets of hypothalamic neuroendocrine neurons. We now report that expression of the gonadotropin-releasing hormone (GnRH) gene, which controls sexual development, is regulated by the POU protein SCIP/Oct- 6/Tst-1. Reverse transcriptase PCR cloning and RNase protection assays demonstrated the presence of SCIP/Oct-6/Tst-1 mRNA in the GnRH-producing neuronal cell line GT1-7. The physiological relevance of this regulatory, activity was suggested by the detection of SCIP/Oct-6/Tst-1 mRNA in a subset of GnRH neurons in the hypothalamus of prepubertal female rats. Coexpression of SCIP/Oct-6/Tst-1 in neuronal cells inhibited rat GnRH (rGnRH) promoter activity via three regions of the proximal rGnRH promoter containing SCIP/Oct-6/Tst-1 binding sites. DNase I footprinting, gel shift assays, and DNA and protein mutagenesis studies indicated that both direct DNA binding and protein-protein interactions are required for SCIP/Oct-6/Tst-1 modulation of GnRH gene expression. Activation of SCIP/Oct-6/Tst-1 expression in terminally differentiated GnRH neurons may be a factor determining the ratio of phenotypically 'inactive' versus 'active' GnRH neurons during postnatal life.

    Original languageEnglish (US)
    Pages (from-to)1652-1665
    Number of pages14
    JournalMolecular and Cellular Biology
    Volume17
    Issue number3
    DOIs
    StatePublished - Mar 1997

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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