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Multiple core homeodomain binding motifs differentially contribute to transcriptional activity of the murine gonadotropin-releasing hormone receptor gene promoter

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Abstract

Multiple homeodomain (Hbox) proteins have been shown to organize expression of key markers of gonadotropes. Nine putative Hbox-binding sites, characterized by the homeospecific TAAT motif, are located within the proximal 600 bp of the murine GnRHR promoter. Homeoproteins bind separate Hbox sites within this promoter, supporting basal- and endocrine-directed transcription. The function of the most proximal sites (Hbox1 and Hbox2) in the murine GnRHR is unknown; thus, understanding of the global contribution of homeospecific TAAT sites to promoter function is incomplete. Site-directed mutagenesis revealed that loss of Hbox2 reduced promoter activity in a cell-specific manner, having no effect in αT3-1 cells but reducing promoter function in LβT2 cells, another gonadotrope-derived cell line representing a later developmental stage. In contrast, eliminating Hbox1 reduced basal activity in both lines. This region displayed specific binding to homeoprotein Oct-1. Mutagenesis of a previously identified Oct-1-binding site in concert with Hbox1 led to further reduction in activity. We suggest that the two most proximal homeodomain-binding sites in the murine GnRHR promoter may regulate the promoter in a developmentally dependent fashion and that Oct-1 acts at multiple but distinct TAAT sites to support basal transcription.

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Acknowledgments

The authors thank Neely Heidorn and Carl Rogers for their help in cloning and transfection assays.

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Authors and Affiliations

  1. Department of Animal and Dairy Science, College of Agricultural and Environmental Sciences, The University of Georgia, 316 Rhodes Center ADS, Athens, GA, 30602, USA

    Clay A. Lents

  2. School of Molecular Biosciences, Washington State University, Box 4234, Pullman, WA, 99164, USA

    Todd A. Farmerie

  3. James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Hungerford Hill Road, Ithaca, NY, 14853, USA

    Brian D. Cherrington

  4. Animal Research and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, 1683 Campus Delivery, Fort Collins, CO, 80523, USA

    Colin M. Clay

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  1. Clay A. Lents
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Correspondence to Colin M. Clay.

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Lents, C.A., Farmerie, T.A., Cherrington, B.D. et al. Multiple core homeodomain binding motifs differentially contribute to transcriptional activity of the murine gonadotropin-releasing hormone receptor gene promoter. Endocr 35, 356–364 (2009). https://doi.org/10.1007/s12020-009-9167-1

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  • DOI: https://doi.org/10.1007/s12020-009-9167-1

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