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 journalArticlepeer-review

    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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