Editorials |
From the Departments of Pathology and Molecular and Cellular Biology, Center for Cardiovascular Development, Baylor College of Medicine, Houston, Tex.
Correspondence to Dr Mark W. Majesky, Dept of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail mmajesky@bcm.tmc.edu
Key Words: smooth muscle serum response factor promoter arterial injury
Studies of the transcriptional control of vascular smooth muscle-specific gene expression have highlighted the importance of a conserved DNA recognition element known as a CArG box. This element has the core sequence CC[AT]6GG and is the binding site for the central MADS box domain of the serum response factor (SRF). All smooth muscle cell (SMC)-specific promoter/enhancer elements characterized to date exhibit a strong dependence upon SRF binding to CArG elements located either in the 5' promoter region, the first intron, or both. It is therefore of considerable interest that a study by Layne et al1 found in this issue of Circulation Research reports the identification of regulatory elements from the mouse aortic carboxypeptidase-like protein (ACLP) promoter that drive reporter gene expression in transgenic mice in a vascular smooth muscle-specific pattern in the absence of a recognizable CArG element.
Mouse Aortic Carboxypeptidase-Like Protein
Mouse ACLP was discovered in a screen for human aortic proteins that interact with the basic helix-loop-helix (bHLH) domain of E47.2 E47, and its related family member E12, are heterodimeric binding partners for myogenic factors (MyoD and myogenin). Heterodimer formation is required for transcriptional activation by myogenic bHLH factors. One of the clones recovered in this screen was a truncated form of human ACLP, which was used to isolate a full-length clone. Sequence analysis of the full-length cDNA revealed that ACLP is a secreted protein that contains a discoidin I-like domain and a catalytically-inactive metallocarboxypeptidase domain. Proteins encoded by the truncated ACLP cDNA bound to E47, whereas full-length ACLP
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