Transforming growth factor-beta response elements of the skeletal alpha-actin gene. Combinatorial action of serum response factor, YY1, and the SV40 enhancer-binding protein, TEF-1.

摘要: Skeletal alpha-actin (SkA) is representative of the cardiac genes that are expressed at high levels in embryonic myocardium, down-regulated after birth, and reactivated by trophic signals including type beta-transforming growth factors (TGF beta). To investigate molecular basis for cardiac-restricted TGF beta-induced SkA transcription, we have undertaken a mutational analysis promoter ventricular myocytes, with emphasis on role three nominal serum response elements. Serum factor (SRF) bifunctional YY1 predominant proteins contacting proximal SRE (SRE1). Mutations SRE1 prevent recognition SRF YY1, or alone, virtually abolish transcription both beta- vehicle-treated cells; mutation distal SREs was ineffective. A which selectively abrogates binding increases basal beta-dependent expression, substantiating predicted as an inhibitor effects. However, efficient requires combinatorial action consensus sites Sp1 SV40 enhancer-binding protein, TEF-1. As isolated motifs, either SRE1- TEF-1-binding function beta Induction required TEF-1 concert, unlike other pathways gene expression.