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A more recent version of this article appeared on October 1, 2004
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Submitted on April 28, 2004
Revised on July 2, 2004
Accepted on July 20, 2004
-Actin Gene Transcription in TGF
1-Activated Myofibroblasts Mediated by Dynamic Interplay Between the Pur Repressor Proteins and Sp1/Smad Co-activators
, , 
, 
,
Departments of *Physiology and Cell Biology and Surgery, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, College of Medicine and Public Health, Columbus, OH 43210; Department of Medicine, College of Medicine, University of Vermont, Colchester, VT 05446
Monitoring Editor: Carl-Henrik Heldin
The mouse vascular smooth muscle 
-actin (SMA) gene enhancer is activated in fibroblasts by TGF
1, a potent mediator of myofibroblast differentiation and wound healing. The SMA enhancer contains tandem sites for the Sp1 transcriptional activator protein and Pur and repressor proteins. We have examined dynamic interplay between these divergent proteins to identify checkpoints for possible control of myofibroblast differentiation during chronic inflammatory disease. A novel element in the SMA enhancer named SPUR was responsible for both basal and TGF1-dependent transcriptional activation in fibroblasts and capable of binding Sp1 and Pur proteins. A novel Sp1:Pur:SPUR complex was dissociated when SMA enhancer activity was increased by TGF1 or Smad protein overexpression. Physical association of Pur proteins with Smad2/3 was observed as was binding of Smads to an upstream enhancer region that undergoes DNA duplex unwinding in TGF1-activated myofibroblasts. Pur repression of the SMA enhancer could not be relieved by TGF1 whereas repression mediated by Pur was partially rescued by TGF1 or overexpression of Smad proteins. Interplay between Pur repressor isoforms and Sp1 and Smad coactivators may regulate SMA enhancer output in TGF1-activated myofibroblasts during episodes of wound repair and tissue remodeling.
These authors contributed equally to this work.
||Corresponding author.
E-mail: strauch1{at}osu.edu
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