A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-β

Authors

Pellegrino Rossi•Gérard Karsenty•Benoît Crombrugghe

Published

February 1, 1988

Abstract

Transforming growth factor-β (TGF-β) increases the steady-state RNA levels of several fibroblast extracellular matrix proteins. Using DNA transfection, we- show that TGF-β stimulates the activity of the mouse α2(I) collagen promoter 5- to 10-fold in mouse NIH 3T3 and rat osteosarcoma cells. Deletion analysis indicates that a segment of this promoter between -350 and -300, overlapping a nuclear factor 1 (NF1) binding site, is needed for TGF-β stimulation. A 3 by substitution mutation abolishing NF1 binding to this site inhibits TGF-β activation. Insertion of this NF1 binding site 5′ to the SV40 early promoter makes the promoter TGF-β inducible, but the 3 by substitution does not. Similarly, when the NF1 binding site at the replication origin of adenovirus 2 and 5 is inserted 5′ to the SV40 promoter, the promoter responds to TGF-β. Therefore an NF1 binding site mediates the transcriptional activation of the mouse α2(I) collagen promoter by TGF-β.