Sequence specific protein binding to and activation of the TGF-β3 promoter through a repeated TCCC motif
| Autor: | Anita B. Roberts, Trevor Williams, Michael B. Sporn, Robert Lafyatis, Fabienne Denhez |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Transcriptional Activation
Molecular Sequence Data Plasma protein binding Biology DNA-binding protein Cell Line Transactivation Transforming Growth Factor beta Genetics Animals Drosophila Proteins Binding site Promoter Regions Genetic Transcription factor Repetitive Sequences Nucleic Acid Regulation of gene expression Messenger RNA Binding Sites Base Sequence DNA Molecular biology DNA-Binding Proteins Gene Expression Regulation Transcription Factor AP-2 Regulatory sequence Mutation Drosophila Transcription Factors |
| Zdroj: | Nucleic Acids Research. 19:6419-6425 |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | We have previously characterized the TGF-beta 3 promoter and shown that the activity of this promoter is highly variable in different cell types. Although the promoter contains a proximal cAMP responsive element, which is critical to basal and forskolin-induced promoter activity, this element is not responsible for the variable, cell-specific regulation of the promoter. In this paper, we identify a 25 base pair sequence in the proximal region of the TGF-beta 3 promoter that binds a novel DNA-binding protein. This region includes the sequence T-CCCTCCCTCCC, (3 x TCCC), and mutation of these T-CCC repeats inhibits protein binding. Further, we show that in the cell line A375, which we have previously shown expresses high levels of TGF-beta 3 mRNA, this region is responsible for mediating high level TGF-beta 3 promoter activity. Immediately 3' to the 3 x TCCC sequence is a consensus AP-2 binding site, however, we show that this region does not bind AP-2, and AP-2 does not transactivate the TGF-beta 3 promoter. Therefore, we provide strong evidence that high level expression of TGF-beta 3 in A375 cells results from transactivation of the TGF-beta 3 promoter by a protein that binds to a repeated TCCC motif in the promoter and suggest that this DNA-binding protein likely also regulates aspects of developmental and tissue-specific expression of this cytokine. |
| Databáze: | OpenAIRE |
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