Published online before print November 14, 2002, doi: 10.1161/01.RES.0000047508.30800.4F
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Submitted on September 5, 2002
Revised on November 6, 2002
Accepted on November 6, 2002
Cell-Specific Regulatory Modules Control Expression of Genes in Vascular and Visceral Smooth Muscle Tissues
April M. Hoggatt ;
From the Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis.
* To whom correspondence should be addressed. E-mail: pherring{at}iupui.edu.
A novel approach with chimeric SM22
/telokin promoters was used to identify gene regulatory modules that are required for regulating the expression of genes in distinct smooth muscle tissues. Conventional deletion or mutation analysis of promoters does not readily distinguish regulatory elements that are required for basal gene expression from those required for expression in specific smooth muscle tissues. In the present study, the mouse telokin gene was isolated, and a 370-bp (-190 to 180) minimal promoter was identified that directs visceral smooth muscle-specific expression in vivo in transgenic mice. The viscera-specific expression of the telokin promoter transgenes is in marked contrast to the reported artery-specific expression of 536-bp minimal SM22 (-475 to 61) promoter transgenes. To begin to identify regulatory elements that are responsible for the distinct tissue-specific expression of these promoters, a chimeric promoter in which a 172-bp SM22 gene fragment (-288 to -116) was fused to the minimal telokin promoter was generated and characterized. The -288 to -116 SM22 gene fragment significantly increased telokin promoter activity in vascular smooth muscle cells in vitro and in vivo. Conversely, a fragment of the telokin promoter (-94 to -49) increased the activity of the SM22 promoter in visceral smooth muscle cells of the bladder. Together, these data demonstrate that both vessel- and viscera-specific regulatory modules exist within smooth muscle-specific promoters and that these modules are used to direct gene expression in subsets of smooth muscle tissues.
Key words: SM22
•
telokin •
gene regulation
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