Hepatocyte nuclear factor 1 alpha activates promoter 1 of the human insulin-like growth factor I gene via two distinct binding sites

Molecular Endocrinology
L A NoltenJ S Sussenbach

Abstract

Expression of the human insulin-like growth factor I (hIGF-I) gene is regulated in a tissue- and developmental stage-specific manner. The hIGF-I gene has two promoters, P1 and P2. P1 is the more active promoter by far in adult liver, the main endocrine source of IGF-I. Recently, we described the involvement of the CAAT/enhancer binding protein family of liver-enriched transcription factors in the regulation of the expression of IGF-I in adult liver. In this study we report on the role of another family of liver-enriched transcription factors in the regulation of IGF-I expression. Hepatocyte nuclear factor 1 alpha (HNF-1 alpha) is shown to transactivate IGF-I P1 in transient transfection experiments performed in Hep3B cells. Bandshift experiments reveal that two distinct regions in P1, located 119 and 282 nucleotides upstream of the transcription start site, can bind HNF-1 alpha with relatively high affinity. Both HNF-1-binding sites are evolutionary well conserved, emphasizing the importance of HNF-1 in the regulation of the IGF-I gene expression. Mutational analysis of the binding sites indicates that both sites are essential for maximal stimulation of P1 by HNF-1 alpha, although the largest contribution stems from the more do...Continue Reading

Citations

Jan 14, 2012·The Journal of Biological Chemistry·Jessica A BonzoFrank J Gonzalez
Dec 17, 2004·Molecular and Cellular Biology·Jennifer E RowlandMichael J Waters
Oct 13, 2009·Molecular Endocrinology·Satyanarayana EleswarapuHonglin Jiang
Jul 31, 2007·The Journal of Thoracic and Cardiovascular Surgery·Yong An, Ying-Bin Xiao
Mar 23, 2017·Endocrinology·Peter Rotwein
May 5, 1998·Molecular and Cellular Biology·Y H LeeF J Gonzalez
Oct 11, 2013·Molecular Endocrinology·Mahalakshmi Santhanam, Dennis J Chia
Dec 18, 2004·Endocrinology·Joel F HabenerMelissa K Thomas

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