Identification of cis- and trans-acting factors regulating the expression of the human insulin receptor gene.

作者: J.K. Lee , J.W. Tam , M.J. Tsai , S.Y. Tsai

DOI: 10.1016/S0021-9258(18)42881-5

关键词: Hormone response elementBinding siteTranscription (biology)Gene expressionBiologyPromoterTranscription factorDeletion MutagenesisMolecular biologyGene

摘要: The functional organization of the human insulin receptor (hIR) promoter was analyzed by deletion mutagenesis and protein-DNA interaction studies. A series mutants expressed transiently in two hepatocytes, HepG2 PLC. results revealed that region between -692 -345 is essential for efficient transcription hIR gene. Multiple trans-acting factors were identified band shift footprinting analyses. Sp1 binds to a cluster GC boxes GGGAGG hexamers locating at -637 -594. Adjacent boxes, there are regions, from -550 -530 -522 -503, which bind novel factors, IRNF-I IRNF-II. These distributed differentially different cell lines. Linker scanning mutations on GC, GA or binding site significantly decreased transcriptional activity, indicating important activity. In addition, we demonstrated glucocorticoid-dependent induction mRNA vivo conferred glucocorticoid response element promoter. Taken together, these imply gene regulated multiple interactions occurring within defined region.

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