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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Jiang, M. S. Tang, Q. Q. Lane, M. D. |
| Description | Author Affiliation: Tang QQ ( Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.); |
| Abstract | During adipocyte differentiation, the expression of C/EBPalpha is activated, which in turn serves to transcriptionally activate numerous adipocyte genes. A previous search for cis elements that regulate transcription of the C/EBPalpha gene led to the identification of a potential repressive element within the proximal 5' flanking region of the gene. Nuclear extracts from 3T3-L1 preadipocytes, but not adipocytes, were found to contain a factor, CUP (C/EBPalpha undifferentiated protein), that binds to this site (the CUP-1 site). In the present investigation, we show that C/EBPalpha promoter-luciferase constructs containing both the proximal 5' flanking and the entire 5' untranslated regions of the gene exhibit an expression pattern during adipocyte differentiation comparable to that of the endogenous C/EBPalpha gene. Mutation of the CUP-1 site in these constructs had little effect on reporter gene expression; however, when this mutation was combined with deletion of the 5' untranslated region, reporter gene expression by preadipocytes was dramatically up-regulated. Consistent with this finding, a second CUP binding site (the CUP-2 site) was identified in the 5' untranslated region. Although mutation of either CUP element in constructs containing both the 5' flanking and 5' untranslated region had little effect on reporter gene transcription, mutation of both CUP elements markedly activated transcription. Thus, it appears that dual CUP regulatory elements repress transcription of the C/EBPalpha gene prior to induction of the adipocyte differentiation program. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 25 |
| Volume Number | 94 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1997-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA-Binding Proteins Genetics Nuclear Proteins 3T3 Cells Adipose Tissue Cytology Metabolism Animals Binding Sites CCAAT-Enhancer-Binding Proteins Cell Differentiation DNA Primers Down-Regulation Drug Effects Genes, Regulator Genes, Reporter Insulin Pharmacology Mice Mutagenesis, Site-Directed Point Mutation Polymerase Chain Reaction Promoter Regions, Genetic Transcription Factor AP-2 Transcription, Genetic Up-Regulation Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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