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Interleukin-6-specific activation of the C/EBPdelta gene in hepatocytes is mediated by Stat3 and Sp1.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 1998 Apr; Vol. 18 (4), pp. 2108-17. - Publication Year :
- 1998
-
Abstract
- C/EBPdelta (CCAAT/enhancer binding protein delta) has been implicated as a regulator of acute-phase response (APR) genes in hepatocytes. Its expression increases dramatically in liver during the APR and can be induced in hepatic cell lines by interleukin-6 (IL-6), an acute-phase mediator that activates transcription of many APR genes. Here we have investigated the mechanism by which C/EBPdelta expression is regulated by IL-6 in hepatoma cells. C/EBPdelta promoter sequences to -125 bp are sufficient for IL-6 inducibility of a reporter gene and include an APR element (APRE) that is essential for IL-6 responsiveness. DNA binding experiments and transactivation assays demonstrate that Stat3, but not Stat1, interacts with this APRE. Two Sp1 sites, one of which is adjacent to the APRE, are required for IL-6 induction and transactivation by Stat3. Thus, Stat3 and Sp1 function cooperatively to activate the C/EBPdelta promoter. Replacement of the APRE with Stat binding elements (SBEs) from the ICAM-1 or C/EBPbeta promoter, both of which recognize both Stat1 and Stat3, confers responsiveness to gamma interferon, a cytokine that selectively activates Stat1. Sequence comparisons suggest that the distinct Stat binding specificities of the C/EBPdelta and C/EBPbeta SBEs are determined primarily by a single base pair difference. Our findings indicate that the cytokine specificity of C/EBPdelta gene expression is governed by the APRE sequence.
- Subjects :
- Acute-Phase Reaction genetics
Base Sequence
CCAAT-Enhancer-Binding Protein-delta
Chromosome Mapping
Cloning, Molecular
Humans
Molecular Sequence Data
Promoter Regions, Genetic
STAT1 Transcription Factor
STAT3 Transcription Factor
Transcriptional Activation
Tumor Cells, Cultured
Acute-Phase Proteins metabolism
CCAAT-Enhancer-Binding Proteins
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Gene Expression Regulation
Interleukin-6 physiology
Liver metabolism
Nuclear Proteins genetics
Sp1 Transcription Factor metabolism
Trans-Activators metabolism
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 18
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 9528783
- Full Text :
- https://doi.org/10.1128/MCB.18.4.2108