The liver-specific promoter of the human insulin-like growth factor II gene is activated by CCAAT/enhancer binding protein (C/EBP).
The human gene coding for insulin-like growth factor II (IGF-II) contains four promoters (P1-P4), that are subjected to tissue-specific and development-dependent regulation. Expression of promoter P1 is detected only in adult liver tissue, whereas promoter P3 is the major IGF-II promoter in fetal liver and is further expressed in other fetal tissues and in adult non-hepatic tissues. C/EBP is a tissue- and development-specific transcription factor that is expressed predominantly in adult liver, adipose tissue and lung. The effect of C/EBP on the expression of constructs containing IGF-II promoter P1 or P3 linked to the luciferase gene was investigated in cotransfection assays using Hep3B cells. We found that promoter P1 can be activated by C/EBP, whereas this transcription factor has no effect on the expression of promoter P3. By gel retardation and DNasel footprinting it was demonstrated that C/EBP can bind to a region of P1 located between 82 and 109 basepairs upstream of the cap site. Furthermore, we showed that deletion of this C/EBP binding region strongly reduces the ability of C/EBP to stimulate transcription from P1. These results indicate that C/EBP is a major component in the specific activation of the human IGF-II promoter P1 in adult liver.
van Dijk
M A
MA
Laboratory for Physiological Chemistry, State University of Utrecht, The Netherlands.
Rodenburg
R J
RJ
Holthuizen
P
P
Sussenbach
J S
JS
D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008099:Liver; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*; D014162:Transfection / Q000235:genetics
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D007335:Insulin-Like Growth Factor II; D008156:Luciferases