Transcriptional regulation of the human KiSS1 gene

Johanna K. Mueller, Anja Dietzel, Alejandro Lomniczi, Alberto Loche, Katrin Tefs, Wieland Kiess, Thomas Danne, Sergio R. Ojeda, Sabine Heger

    Research output: Contribution to journalArticle

    48 Scopus citations

    Abstract

    Kisspeptin, the product of the KiSS1 gene, has emerged as a key component of the mechanism by which the hypothalamus controls puberty and reproductive development. It does so by stimulating the secretion of gonadotropin releasing hormone (GnRH). Little is known about the transcriptional control of the KiSS1 gene. Here we show that a set of proteins postulated to be upstream components of a hypothalamic network involved in controlling female puberty regulates KiSS1 transcriptional activity. Using RACE-PCR we determined that transcription of KiSS1 mRNA is initiated at a single transcription start site (TSS) located 153-156. bp upstream of the ATG translation initiation codon. Promoter assays performed using 293 MSR cells showed that the KiSS1 promoter is activated by TTF1 and CUX1-p200, and repressed by EAP1, YY1, and CUX1-p110. EAP1 and CUX-110 were also repressive in GT1-7 cells. All four TFs are recruited in vivo to the KiSS1 promoter and are expressed in kisspeptin neurons. These results suggest that expression of the KiSS1 gene is regulated by trans-activators and repressors involved in the system-wide control of mammalian puberty.

    Original languageEnglish (US)
    Pages (from-to)8-19
    Number of pages12
    JournalMolecular and Cellular Endocrinology
    Volume342
    Issue number1-2
    DOIs
    StatePublished - Aug 6 2011

    Keywords

    • CUX1
    • EAP1
    • Gene transcription
    • TTF1
    • Transcription factors
    • YY1

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Endocrinology

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  • Cite this

    Mueller, J. K., Dietzel, A., Lomniczi, A., Loche, A., Tefs, K., Kiess, W., Danne, T., Ojeda, S. R., & Heger, S. (2011). Transcriptional regulation of the human KiSS1 gene. Molecular and Cellular Endocrinology, 342(1-2), 8-19. https://doi.org/10.1016/j.mce.2011.04.025