Transforming growth factor-beta stimulates alpha 2(I) collagen gene expression through a cis-acting element that contains an Sp1-binding site.

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DOI: 10.1016/s0021-9258(17)36699-1 Publication Date: 2021-01-04T13:43:56Z
ABSTRACT
Transforming growth factor-pl (TGF-P) is a strong and rapid inducer of several genes coding for extracellular matrix components, such as type I collagen.W e report here that TGF-P stimulates transcription the human (u2(I) collagen gene (COLlA2) promoter by increasing affinity an Spl-containing protein complex its cognate DNA-binding site.Cell transfection experiments mapped TGF-P-responsive element (TbRE) COLlA2 to 131 bp region contains at least two cis-acting elements.Insertion TbRE upstream thymidine kinase conferred TGF-f.3 inducibility otherwise unresponsive promoter.Footprinting assays revealed neighboring proteinbound sequences, termed Box 3A B. Within Spl recognition sequence whose structural integrity required nuclear binding in vitro, uiuo.Gel mobility shift documented increased proteins from TGF-P-treated cells compared with those TGF-P-untreated fibroblasts.There was, however, no increase alone or oligonucleotide.Thus, results strongly suggest functional interaction between other components mediating TGF-/3 stimulation expression.
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