Transcriptional regulation of the human growth hormone receptor (hGHR) gene V2 promoter by transcriptional activators and repressor.

Molecular Endocrinology
Yuhong WeiCynthia Gates Goodyer

Abstract

The V2 transcript is the major ubiquitously expressed human GH receptor (hGHR) mRNA in all tissues examined to date. In a previous investigation, we defined the V2 promoter as TATA-less and exhibiting many characteristics of a housekeeping gene promoter. We also demonstrated that its basal activity is determined by several different cis-regulatory regions within both the promoter and the V2 exon. In the present study, we used luciferase-reporter, site-directed mutagenesis, gel shift, chromatin immunoprecipitation, and quantitative RT-PCR assays to investigate the ability of certain transcription factors to regulate hGHR V2 transcription through these regions in mammalian cells, including human adipocytes. Ets1 was found to transactivate the V2 proximal promoter through specific Ets sites. Two CCAAT/enhancer-binding protein (C/EBP) family members [C/EBP-homologous protein (CHOP) and C/EBPbeta] enhanced V2 transcription via different pathways: indirectly, by association with a V2 exon region (CHOP), and directly, using a V2 proximal promoter noncanonical binding site (C/EBPbeta). The Notch signaling mediator, Hes1, potently suppressed V2 promoter activity through interaction with two Hes sites within the V2 exon. We propose that ...Continue Reading

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Citations

Mar 10, 2011·International Journal of Obesity : Journal of the International Association for the Study of Obesity·A ErmanC G Goodyer
Sep 9, 2009·General and Comparative Endocrinology·Mark A Sheridan, Alison L Hagemeister
Jun 19, 2013·Biochimica Et Biophysica Acta·Christopher M CarmeanMatthew J Brady
May 20, 2008·Advances in Applied Microbiology·R E ParalesJ L Ditty
Jul 30, 2014·Molecular Endocrinology·Samar Elzein, Cynthia Gates Goodyer

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