Transcriptional regulation of the human insulin receptor promoter.
The ability of the human insulin receptor promoter to direct expression of a linked chloramphenicol acetyltransferase gene was assessed in transient transfections into HepG2 and Hela cells. A 5'-deletional analysis of the promoter showed that regions between -646 and -489 were important for the activity of the proximal promoter. In addition, a possible negative regulatory element was identified between -1311 and -877 and a positive element between -1823 and -1311. DNase I footprint and gel retardation analysis showed that multiple factors bind to the human insulin receptor promoter. In particular, DNase I protection patterns were observed over the Sp1 sites at -620 to -599 and -438 to -392, a TC box at -533, four homopyrimidine/homopurine sites clustered around -1150, and a site at -1420 that contains the motif TGGCCC which has been shown to bind the liver-specific transcription factor LF-A1.
Cameron
K E
KE
Department of Medicine, University of California, San Diego, La Jolla 92093.
Resnik
J
J
Webster
N J
NJ
D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D003850:Deoxyribonuclease I; D005786:Gene Expression Regulation; D006367:HeLa Cells; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D015500:Chloramphenicol O-Acetyltransferase; D011972:Receptor, Insulin; D003850:Deoxyribonuclease I