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

Ponticos, M; Harvey, C; Ikeda, T; Abraham, D; Bou-Gharios, G; (2009) JunB mediates enhancer/promoter activity of COL1A2 following TGF-beta induction. NUCLEIC ACIDS RES , 37 (16) 5378 - 5389. 10.1093/nar/gkp544. Gold open access

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.

Type: Article
Title: JunB mediates enhancer/promoter activity of COL1A2 following TGF-beta induction
Open access status: An open access publication
DOI: 10.1093/nar/gkp544
Keywords: GROWTH-FACTOR-BETA, FAR-UPSTREAM ENHANCER, ALPHA 2(I) COLLAGEN, GENE-EXPRESSION, TRANSGENIC MICE, MESENCHYMAL TRANSITION, ELECTROSTATIC INTERACTIONS, FIBROBLASTS, PROMOTER, FIBROSIS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/1305475
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