Expression of the smooth muscle cell calponin gene marks the early cardiac and smooth muscle cell lineages during mouse embryogenesis
Expression of the smooth muscle cell calponin gene marks the early cardiac and smooth muscle cell lineages during mouse embryogenesis
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DOI：
10.1074/jbc.271.12.7095
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发表时间：
1996-03-22
影响因子：
4.8
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Miano, JM;Olson, EN
虽然有几个基因被认为是血管平滑肌细胞（SMC）分化的标志物，但很少有人在哺乳动物中严格测试SMC特异性，特别是在不同肌肉基因程序之间存在相当大的重叠的发育过程中。在这里，我们描述的时空表达模式的SMC钙调蛋白基因（以前高或基本钙调蛋白）在小鼠胚胎发育和成年小鼠组织和细胞系。而SMC钙调蛋白mRNA的表达仅限于SMC在成人组织中，在早期胚胎发生，SMC钙调蛋白转录表达整个发展中的心管，以及在分化的SMC。在缺乏共有TATAA或起始元件的情况下，SMC钙调蛋白基因的转录起始于两个紧密并列的位点。瞬时转染实验表明，高水平的SMC calponin启动子活性所需的5'端序列不超过549个核苷酸。与SMC钙调蛋白mRNA表达的严格细胞类型特异性相反，SMC钙调蛋白启动子在不表达内源性SMC钙调蛋白基因的几种细胞系中显示出活性。这些结果表明，SMC钙调蛋白响应心脏和平滑肌基因调控程序，并表明心脏和平滑肌细胞谱系可能在胚胎发生早期共享一个共同的基因调控程序，随着心脏的成熟而分化。分离的SMC钙调蛋白启动子比内源性SMC钙调蛋白基因在更广泛的细胞中具有活性，这一发现也表明，SMC钙调蛋白表达的细胞特异性调节中涉及长程抑制或更高级的调节机制。
Although several genes are considered markers for vascular smooth muscle cell (SMC) differentiation, few have been rigorously tested for SMC specificity in mammals, particularly during development where considerable overlap exists between different muscle gene programs. Here we describe the temporospatial expression pattern of the SMC calponin gene (formerly hi or basic calponin) during mouse embryogenesis and in adult mouse tissues and cell lines. Whereas SMC calponin mRNA expression is restricted exclusively to SMCs in adult tissues, during early embryogenesis, SMC calponin transcripts are expressed throughout the developing cardiac tube as well as in differentiating SMCs. Transcription of the SMC calponin gene initiates at two closely juxtaposed sites in the absence of a consensus TATAA or initiator element. Transient transfection assays in cultured SMC demonstrated that high level SMC calponin promoter activity required no more than 549 nucleotides of 5' sequence. In contrast to the strict cell type-specificity of SMC calponin mRNA expression, the SMC calponin promoter showed activity in several cell lines that do not express the endogenous SMC calponin gene. These results demonstrate that SMC calponin responds to cardiac and smooth muscle gene regulatory programs and suggest that the cardiac and smooth muscle cell lineages may share a common gene regulatory program early in embryogenesis, which diverges as the heart matures. The finding that the isolated SMC calponin promoter is active in a wider range of cells than the endogenous SMC calponin gene also suggests that long-range repression or higher order regulatory mechanism(s) are involved in cell-specific regulation of SMC calponin expression.