Multiple proteins bind the insulin response element in the human IGFBP-1 promoter.
An insulin response element (IRE) has been identified approximately 100 base pairs (bp) 5' to the transcription start site of the human insulin-like growth factor binding protein-1 (hIGFBP-1) gene. This cis element appears crucial to the multihormonal regulation of hIGFBP-1 expression in liver, since (i) an intact IRE is required for maximal stimulation of hIGFBP-1 promoter activity by dexamethasone, and (ii) the IRE confers insulin inhibition of both basal and dexamethasone-stimulated hIGFBP-1 promoter activity. Further progress in understanding how the IRE confers insulin and glucocorticoid effects requires identification of transcription factors confering effects of these hormones. D-site binding protein (DBP), and members of the hepatic nuclear factor 3 (HNF 3) and high mobility group I/Y (HMG I/Y) protein families, each known to bind DNA elements similar in sequence to the IRE, were tested for IRE binding. DBP, HMGI and HNF 3 beta each protected the hIGFBP-1 IRE from DNAseI digestion. Additional studies are required to establish whether binding of any of these proteins to the IRE is important to the regulation of hIGFBP-1 expression by insulin and/or glucocorticoids.
Powell
D R
DR
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Allander
S V
SV
Scheimann
A O
AO
Wasserman
R M
RM
Durham
S K
SK
Suwanichkul
A
A
D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D025741:HMGA1a Protein; D051542:Hepatocyte Nuclear Factor 3-beta; D006609:High Mobility Group Proteins / Q000378:metabolism; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics*; D016350:Leucine Zippers; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
C063898:DBP protein, human; D004268:DNA-Binding Proteins; C496502:FOXA2 protein, human; D006609:High Mobility Group Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D009687:Nuclear Proteins; D014157:Transcription Factors; D025741:HMGA1a Protein; D051542:Hepatocyte Nuclear Factor 3-beta; C075372:insulin response element binding protein, human; D004247:DNA; D003850:Deoxyribonuclease I