Substitution of the degenerate smooth muscle (SM) alpha-actin CC(A/T-rich)6GG elements with c-fos serum response elements results in increased basal expression but relaxed SM cell specificity and reduced angiotensin II inducibility.

The Journal of Biological Chemistry
M B HautmannGary K Owens

Abstract

We have previously demonstrated that both CC(A/T-rich)6GG (CArG) elements A and B of the smooth muscle (SM) alpha-actin promoter are required for smooth muscle cell (SMC)-specific expression and angiotensin II (AII)-induced stimulation. Moreover, results provided evidence that AII responsiveness of SM alpha-actin was at least partially dependent on modulation of serum response factor (SRF) binding to the SM alpha-actin CArGs by the homeodomain containing protein, MHox. The goal of the present study was to investigate whether the degeneracy of the SM alpha-actin CArGs (both contain a Gua or Cyt substitution in their A/T-rich center) and their reduced SRF binding activity as compared with c-fos serum response element (SRE) is important for conferring cell type-specific expression and AII responsiveness. Transient transfection assays using SM alpha-actin reporter gene constructs in which the endogenous SM alpha-actin CArGs were replaced by c-fos SREs demonstrated the following: 1) relaxation of cell-specific expression, 2) a 50% reduction in AII responsiveness, and 3) reduced ability to be transactivated by MHox. In addition, we also showed that the position of the SM alpha-actin CArGs was important in that interchanging them abol...Continue Reading

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Citations

Jun 6, 2003·Journal of Molecular and Cellular Cardiology·Joseph M Miano
Mar 13, 2012·Cardiovascular Research·Delphine Gomez, Gary K Owens
Feb 18, 2011·Genome Génome / Conseil National De Recherches Canada·Xia ShenShan Miao
Jul 21, 2011·Physiological Genomics·Craig C BensonJoseph M Miano
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May 17, 2005·Journal of Thrombosis and Haemostasis : JTH·C P Mack, J S Hinson
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Feb 9, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·M BuckM Chojkier
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