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JunB mediates enhancer/promoter activity of COL1A2 following TGF-beta induction.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2009 Sep; Vol. 37 (16), pp. 5378-89. Date of Electronic Publication: 2009 Jun 26. - Publication Year :
- 2009
-
Abstract
- Transcriptional control of the genes coding for collagen type I is regulated by a complex interaction between a distal enhancer and a proximal promoter. In this study, we have dissected the molecular mechanism of this interaction by defining a specific sequence within the enhancer that respond in fibroblasts to transforming growth factor-beta (TGF-beta). We show that TGF-beta activates COL1A2 gene via a non-canonical (Smad-independent) signalling pathway, which requires enhancer/promoter co-operation. This interaction involves exchange of cJun/Jun B transcription factor occupancy of a critical enhancer site resulting in the stabilization of enhancer/promoter coalescence. Moreover, using transgenesis, we show that interference in this mechanism results in the abolition of COL1A2 fibroblast expression in vivo. These data are therefore relevant to the control of collagen type I in vivo both in embryonic development, in adult connective tissue homeostasis, and in tissue repair and scarring pathologies.
- Subjects :
- Animals
Cells, Cultured
Collagen biosynthesis
Collagen Type I
Gene Expression Regulation
Humans
Mice
Mice, Transgenic
NIH 3T3 Cells
Response Elements
Transcription Factor AP-1 metabolism
Collagen genetics
Enhancer Elements, Genetic
Promoter Regions, Genetic
Proto-Oncogene Proteins c-jun metabolism
Transforming Growth Factor beta pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 37
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 19561194
- Full Text :
- https://doi.org/10.1093/nar/gkp544