Regulation of type I collagen genes expression.
Type I collagen is the major component of many extracellular matrices, and its accumulation characterizes most fibrotic processes. It is synthesized by a small number of discrete cell types, including fibroblasts, osteoblasts and odontoblasts. Analysis of transgenic mice harbouring different segments of the promoters of the mouse pro-alpha1 (I) and pro-alpha2 (I) genes has led to the conclusion that this tissue-specific expression is controlled by different cis-acting elements which are responsible for the expression of type I collagen genes in different type I collagen-producing cells. Transacting factors which bind to these different tissue-specific elements are still unknown, but they probably act by modifying the chromatin structure. In fibroblastic cells, various soluble molecules can modulate the transcription of type I collagen genes. Analysis of the pro-alpha1 (I) and pro-alpha2 (I) proximal promoters has led to the identification of different cis-acting elements which can modulate the expression of reporter genes, in transfection experiments. Among these cis-acting elements, a sequence located between -378 and -183 bp in the human pro-alpha2 (I) promoter appears to mediate the transcriptional effects of transforming growth factor-beta. It binds a large multimeric complex which contains Sp1, as well as AP1 and other DNA-binding proteins which have not yet been identified.
Rossert
J
J
INSERM U.489 and Department of Nephrology, Paris VI University, Assistance Publique-H pitaux de Paris, France.
Terraz
C
C
Dupont
S
S
D000818:Animals; D003094:Collagen / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008233:Lymphotoxin-alpha / Q000502:physiology; D011347:Procollagen / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D020218:Response Elements / Q000502:physiology; D013237:Stereoisomerism
D008233:Lymphotoxin-alpha; D011347:Procollagen; D003094:Collagen