Human growth hormone receptor gene expression is regulated by Gfi-1/1b and GAGA cis-elements.
Human growth hormone receptor (hGHR) gene regulation is complex: mRNAs are transcribed from multiple variant (V) 5'UTR exons, several ubiquitously while others only in the postnatal hepatocyte. The liver-specific V1 exon promoter contains Gfi-1/1b repressor sites adjacent to a GAGA box, a GH response element (GHRE) in several mammalian genes. GAGA boxes are also present in the ubiquitously expressing V3 exon promoter. Heterologous sites in bovine, ovine and murine GHR genes suggest conserved roles. GAGA factor stimulated V1 and V3 promoters while Gfi-1/1b repressed basal and GAF-stimulated V1 transcription. HGH treatment of HepG2 cells resulted in a new complex forming with V3 GAGA elements, suggesting a functional GHRE. Data suggest liver-specific V1 transcription is regulated by inhibitory Gfi-1/1b and stimulatory GAGA cis-elements and Gfi-1/1b may control the lack of V1 expression in fetal liver, hepatic tumours and non-hepatic tissues. In addition, hGH may regulate hGHR expression through V3 GAGA boxes.
Department of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
Gurvinder
G
Kenth
Svetlana
S
Puzhko
Cynthia Gates
CG
Goodyer
D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000166:cytology / Q000196:embryology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D020218:Response Elements; D050799:STAT5 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C498275:GFI1 protein, human; C111977:GFI1B protein, human; D011518:Proto-Oncogene Proteins; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D014157:Transcription Factors; C063460:Trl protein, Drosophila