Col1a2 enhancer regulates collagen activity during development and in adult tissue repair.
An enhancer region in the type I collagen alpha 2 chain (pro-Col1a2) promoter has been previously identified approximately -17 kb away from the transcription start site. This upstream region termed the far-upstream-enhancer contains three DNAse I hypersensitive sites and has been shown to be conserved between mouse and human genes. In this study, we used transgenic mice harbouring the complete promotor sequence of the pro-Col1a2 gene up to -17 kb to examine the role of this enhancer in the expression and regulation of the collagen gene during development and in adult tissues pre and post injury. By careful histological mapping of the collagen type I endogenous gene distribution with that of the transgene driven by the mouse far upstream enhancer, we are able to show that in early days of collagen expression, E8.5-9.5, the endogenous gene preceded transgene expression. However, by E11.5 the overall pattern becomes synchronous with a few exceptions. In adult tissue, both endogenous and transgene expression are attenuated and both are reactivated in parallel in various organs by physical injury or fibrogenic cytokine injection. These findings suggest that the enhancer is central to the activation of the collagen type I and that mice harbouring this enhancer/reporter provide a useful model to follow collagen gene transcription activity and for investigating cellular activity in tissue fibrosis.
Ponticos
Markella
M
Muscle Cell Biology Group, MRC Clinical Science Centre, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
Abraham
David
D
Alexakis
Catherine
C
Lu
Qi-Long
QL
Black
Carol
C
Partridge
Terence
T
Bou-Gharios
George
G
D000818:Animals; D003094:Collagen / Q000235:genetics* / Q000378:metabolism*; D024042:Collagen Type I; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004742:Enhancer Elements, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005865:Gestational Age; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012867:Skin / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D024042:Collagen Type I; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen