Opposite Smad and chicken ovalbumin upstream promoter transcription factor inputs in the regulation of the collagen VII gene promoter by transforming growth factor-β Journal Article
| Authors: | Calonge, M. J.; Seoane, J.; Massagué, J. |
| Article Title: | Opposite Smad and chicken ovalbumin upstream promoter transcription factor inputs in the regulation of the collagen VII gene promoter by transforming growth factor-β |
| Abstract: | A critical component of the epidermal basement membrane, collagen type VII, is produced by keratinocytes and fibroblasts, and its production is stimulated by the cytokine transforming growth factor-β (TGF-β). The gene, COL7A1, is activated by TGF-β via Smad transcription factors in cooperation with AP1. Here we report a previously unsuspected level of complexity in this regulatory process. We provide evidence that TGF-β may activate the COL7A1 promoter by two distinct inputs operating through a common region of the promoter. One input is provided by TGF-β-induced Smad complexes via two Smad binding elements that function redundantly depending on the cell type. The second input is provided by relieving the COL7A1 promoter from chicken ovalbumin upstream promoter transcription factor (COUP-TF) -mediated transcriptional repression. We identified COUP-TFI and -TFII as factors that bind to the TGF-β-responsive region of the COL7A1 promoter in an expression library screening. COUP-TFs bind to a site between the two Smad binding elements independently of Smad or AP1 and repress the basal and TGF-β-stimulated activities of this promoter. We provide evidence that endogenous COUP-TF activity represses the COL7A1 promoter. Furthermore, we show that TGF-β addition causes a rapid and profound down-regulation of COUP-TF expression in keratinocytes and fibroblasts. The results suggest that TGF-ν signaling may exert tight control over COL7A1 by offsetting the balance between opposing Smad and COUP-TFs. |
| Keywords: | signal transduction; controlled study; promoter region; dna-binding proteins; nonhuman; animal cell; animals; mice; genes; basement membrane; smad protein; transforming growth factor beta; transcription factor; keratinocyte; animalia; transcription factors; gene expression regulation; cytokines; protein processing; transcription regulation; molecular sequence data; gene repression; collagen; fibroblast; smad proteins; base sequence; trans-activators; cell stimulation; biochemistry; receptors, steroid; biological organs; 3t3 cells; cells; receptor down regulation; chicken; promoter regions (genetics); ovalbumin; chicken ovalbumin upstream promoter transcription factor; humans; priority journal; article; chicken ovalbumin; collagen type 7; collagen metabolism; collagen type vii; coup transcription factors; gallus gallus |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 279 |
| Issue: | 22 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2004-05-28 |
| Start Page: | 23759 |
| End Page: | 23765 |
| Language: | English |
| DOI: | 10.1074/jbc.M402178200 |
| PROVIDER: | scopus |
| PUBMED: | 15047696 |
| DOI/URL: | |
| Notes: | J. Biol. Chem. -- Cited By (since 1996):11 -- Export Date: 16 June 2014 -- CODEN: JBCHA -- Source: Scopus |
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