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Publication : JunB mediates enhancer/promoter activity of COL1A2 following TGF-beta induction.

First Author  Ponticos M Year  2009
Journal  Nucleic Acids Res Volume  37
Issue  16 Pages  5378-89
PubMed ID  19561194 Mgi Jnum  J:173026
Mgi Id  MGI:5009487 Doi  10.1093/nar/gkp544
Citation  Ponticos M, et al. (2009) JunB mediates enhancer/promoter activity of COL1A2 following TGF-beta induction. Nucleic Acids Res 37(16):5378-89
abstractText  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.
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