Title |
Genomic Cloning and Promoter Analysis of Aortic Preferentially Expressed Gene-1 IDENTIFICATION OF A VASCULAR SMOOTH MUSCLE-SPECIFIC PROMOTER MEDIATED BY AN E BOX MOTIF*
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Published in |
Journal of Biological Chemistry, May 1999
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DOI | 10.1074/jbc.274.20.14344 |
Pubmed ID | |
Authors |
Chung-Ming Hsieh, Shaw-Fang Yet, Matthew D. Layne, Masafumi Watanabe, Audrey M. Hong, Mark A. Perrella, Mu-En Lee |
Abstract |
Aortic preferentially expressed gene-1 (APEG-1) was originally identified as a 1.4-kilobase (kb) transcript preferentially expressed in differentiated vascular smooth muscle cells (VSMC). Its expression is markedly down-regulated in de-differentiated VSMC, suggesting a role for APEG-1 in VSMC differentiation. We have now determined that APEG-1 is a single-copy gene in the human, rat, and mouse genomes and have mapped human APEG-1 to chromosome 2q34. To study the molecular mechanisms regulating its expression, we characterized the genomic organization and promoter of mouse APEG-1. APEG-1 spans 4.5 kb in the mouse genome and is composed of five exons. Using reporter gene transfection analysis, we found that a 2. 7-kb APEG-1 5'-flanking sequence directed a high level of promoter activity only in VSMC. Its activity was minimal in five other cell types. A repressor region located within an upstream 685-base pair sequence suppressed the activity of this 2.7-kb promoter. Further deletion and mutation analyses identified an E box motif as a positive regulatory element, which was bound by nuclear protein prepared from VSMC. In conjunction with its flanking sequence, this E box motif confers VSMC-specific enhancer activity to a heterologous SV40 promoter. To our knowledge, this is the first demonstration of an E box motif that mediates gene expression restricted to VSMC. |
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