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PMID: 1620607 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The liver-specific promoter of the human insulin-like growth factor II gene is activated by CCAAT/enhancer binding protein (C/EBP).

Nucleic acids research ·Vol. 20 ·No. 12 ·1992-06-25 ·Pages 3099-104

van Dijk MA, Rodenburg RJ, Holthuizen P, Sussenbach JS

Abstract

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.

Related Genes
IGF-II
MeSH Terms
Base Sequence CCAAT-Enhancer-Binding Proteins Cell Line DNA-Binding Proteins/genetics,metabolism Humans Insulin-Like Growth Factor II/genetics Liver Luciferases/genetics,metabolism Molecular Sequence Data Nuclear Proteins/genetics,metabolism Oligodeoxyribonucleotides/genetics Plasmids/genetics Promoter Regions, Genetic/genetics Recombinant Fusion Proteins/genetics,metabolism Transcriptional Activation/genetics Transfection/genetics
Chemicals
CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins Nuclear Proteins Oligodeoxyribonucleotides Recombinant Fusion Proteins Insulin-Like Growth Factor II Luciferases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
van Dijk M A
Laboratory for Physiological Chemistry, State University of Utrecht, The Netherlands.
Rodenburg R J
Holthuizen P
Sussenbach J S
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/20.12.3099
Published
1992-06-25
Pages
3099-104
Language
English
Region
England
NLM ID
0411011
PMCID
PMC312444
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/20.12.3099 PMC Full Text View journal details
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