HRC is a direct transcriptional target of MEF2 during cardiac, skeletal, and arterial smooth muscle development in vivo
HRC is a direct transcriptional target of MEF2 during cardiac, skeletal, and arterial smooth muscle development in vivo
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DOI：
10.1128/mcb.24.9.3757-3768.2004
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发表时间：
2004-05-01
影响因子：
5.3
通讯作者：
Black, BL
中科院分区：
文献类型：
--
作者：
Anderson, JP;Dodou, E;Black, BL
HRC基因编码富含组氨酸的钙结合蛋白，该蛋白存在于心脏和骨骼肌交界肌浆网（SR）的管腔以及动脉平滑肌的钙小体中。HRC在心肌、骨骼肌和平滑肌中的表达提出了一种共同的转录机制控制其在所有三种肌肉细胞类型中的表达的可能性。在这项研究中，我们从HRC基因中鉴定了一个转录增强子，足以指导lacZ在转基因小鼠内源性HRC表达模式中的表达。HRC增强子包含一个小的，高度保守的序列，在所有三种肌肉谱系中都需要表达。在这个保守区域是肌细胞增强因子2 （MEF2）蛋白的共识位点，我们发现MEF2有效结合，并且在体内所有三种肌肉谱系中都需要转基因表达。此外，整个HRC增强子序列缺乏任何可识别的CArG基序，这是血清反应因子（SRF）的结合位点，我们发现该增强子不会被SRF激活。因此，这些研究确定了HRC增强子是平滑肌中第一个依赖mef2、不依赖carg的转录靶点，并首次分析了SR基因在体内的转录调控。
The HRC gene encodes the histidine-rich calcium-binding protein, which is found in the lumen of the junctional sarcoplasmic reticulum (SR) of cardiac and skeletal muscle and within calciosomes of arterial smooth muscle. The expression of HRC in cardiac, skeletal, and smooth muscle raises the possibility of a common transcriptional mechanism governing its expression in all three muscle cell types. In this study, we identified a transcriptional enhancer from the HRC gene that is sufficient to direct the expression of lacZ in the expression pattern of endogenous HRC in transgenic mice. The HRC enhancer contains a small, highly conserved sequence that is required for expression in all three muscle lineages. Within this conserved region is a consensus site for myocyte enhancer factor 2 (MEF2) proteins that we show is bound efficiently by MEF2 and is required for transgene expression in all three muscle lineages in vivo. Furthermore, the entire HRC enhancer sequence lacks any discernible CArG motifs, the binding site for serum response factor (SRF), and we show that the enhancer is not activated by SRF. Thus, these studies identify the HRC enhancer as the first MEF2-dependent, CArG-independent transcriptional target in smooth muscle and represent the first analysis of the transcriptional regulation of an SR gene in vivo.