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PMID: 7862113 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Autoregulation of the human C/EBP alpha gene by stimulation of upstream stimulatory factor binding.

Molecular and cellular biology ·Vol. 15 ·No. 3 ·1995-03-00 ·Pages 1192-202

Timchenko N, Wilson DR, Taylor LR, Abdelsayed S, Wilde M, Sawadogo M, Darlington GJ

Abstract

The human C/EBP alpha gene promoter shares significant sequence homology with that of the mouse but has a different mechanism of autoregulation. Activation of the murine promoter by direct binding of C/EBP alpha to a site within 200 bp of the transcriptional start was shown to elevate activity by approximately threefold (R. J. Christy, K. H. Kaestner, D. E. Geiman, and M. D. Lane, Proc. Natl. Acad. Sci. USA 88:2593-2597, 1991; K. Legraverend, P. Antonson, P. Flodby, and K. G. Xanthapoulos, Nucleic Acids Res. 21:1735-1742, 1993). Unlike its murine counterpart, the human C/EBP alpha gene promoter does not contain a cis element that binds the C/EBP alpha protein. Neither C/EBP alpha nor C/EBP beta (NF-Il-6) binds the human C/EBP alpha promoter within 437 bp. However, cotransfection studies show that C/EBP alpha stimulates transcription of a reporter gene driven by 437 bp of the C/EBP alpha promoter. Our studies show that the human C/EBP alpha protein stimulates USF to bind to a USF consensus element within C/EBP alpha promoter and activates it by two- to threefold. We propose that the human gene employs the ubiquitously expressed DNA-binding protein factor USF to carry out autoregulation. Autoregulation of the human C/EBP alpha promoter was abolished by deletion of the USF binding site, CACGTG. Expression of human C/EBP beta following transfection did not stimulate USF binding. These studies suggest a mechanism whereby tissue-specific autoregulation can be achieved via a trans-acting factor that is expressed in all cell types. Thus, direct binding of the C/EBP alpha protein to the promoter of the C/EBP alpha gene is not required for autoregulation.

MeSH Terms
Amino Acid Sequence Animals Base Sequence CCAAT-Enhancer-Binding Proteins Carcinoma, Hepatocellular Cell Line DNA Primers DNA-Binding Proteins/biosynthesis,genetics Gene Expression Regulation, Neoplastic Homeostasis Humans Immunoblotting Liver Neoplasms Mice Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Proteins/biosynthesis,genetics Oligodeoxyribonucleotides Promoter Regions, Genetic Regulatory Sequences, Nucleic Acid Restriction Mapping Sequence Homology, Nucleic Acid Transcription Factors Tumor Cells, Cultured
Chemicals
CCAAT-Enhancer-Binding Proteins DNA Primers DNA-Binding Proteins Nuclear Proteins Oligodeoxyribonucleotides Transcription Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Timchenko N
Department of Pathology, Baylor College of Medicine, Houston, Texas.
Wilson D R
Taylor L R
Abdelsayed S
Wilde M
Sawadogo M
Darlington G J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.15.3.1192
Published
1995-03-00
Pages
1192-202
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC230342
Subset
IM
Grants
NIDDK NIH HHS · NIDDKD 44080 · United States
NIDDK NIH HHS · NIDDKD 45285 · United States
Databases
GENBANK
S75265
External Links
PubMed source DOI: 10.1128/MCB.15.3.1192 PMC Full Text View journal details
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