Structural and functional characterization of the transforming growth factor beta 3 promoter. A cAMP-responsive element regulates basal and induced transcription
Autor: | R, Lafyatis, R, Lechleider, S J, Kim, S, Jakowlew, A B, Roberts, M B, Sporn |
---|---|
Rok vydání: | 1990 |
Předmět: |
Base Sequence
Transcription Genetic Chimera Swine Molecular Sequence Data Restriction Mapping Transfection DNA-Binding Proteins Mice Species Specificity Transforming Growth Factor beta Protein Biosynthesis Leukocytes Animals Humans Cloning Molecular Cyclic AMP Response Element-Binding Protein Promoter Regions Genetic Chickens Gene Library Plasmids |
Zdroj: | The Journal of biological chemistry. 265(31) |
ISSN: | 0021-9258 |
Popis: | Transforming growth factor beta 3 (TGF-beta 3) has been cloned from humans, chickens, pigs, and mice. Although the specific in vivo roles of this form of TGF-beta are unknown, the pattern of embryonic and tissue-specific expression of TGF-beta 3 suggests that it is involved in embryogenesis and cell differentiation. We have cloned and sequenced the TGF-beta 3 5'-flanking region to study the transcriptional regulation of this gene. Characterization of the 5'-flanking region showed a 1104-base pair 5'-untranslated region, a TATA box 21 bp upstream from the transcription start site, and cAMP-responsive element (CRE) and AP-2 binding site consensus sequences starting at 12 and 24 bp, respectively, upstream from the TATA box. Promoter fragments were cloned into a chloramphenicol acetyltransferase reporter plasmid to study functional activity. Basal transcriptional activity of the promoter was regulated by multiple upstream elements including the CRE and the AP-2 site. The CRE was important for both basal and forskolin induction of promoter activity. The TGF-beta 3 promoter was found to be strikingly dissimilar to the TGF-beta 1 promoter. Since the TGF-beta s have activity in promoting or inhibiting proliferation and differentiation of multiple cell types, it seems likely that the differential and tissue-specific transcriptional regulation of these genes is of fundamental importance in the induction and maintenance of differentiated cell types in various tissues. |
Databáze: | OpenAIRE |
Externí odkaz: |