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首页> 外文期刊>Molecular and Cellular Biology >The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells.
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The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells.

机译：GATA-4转录因子可在非肌肉细胞中激活心肌特异性肌钙蛋白C启动子增强子。

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摘要

The unique contractile phenotype of cardiac myocytes is determined by the expression of a set of cardiac muscle-specific genes. By analogy to other mammalian developmental systems, it is likely that the coordinate expression of cardiac genes is controlled by lineage-specific transcription factors that interact with promoter and enhancer elements in the transcriptional regulatory regions of these genes. Although previous reports have identified several cardiac muscle-specific transcriptional elements, relatively little is known about the lineage-specific transcription factors that regulate these elements. In this report, we demonstrate that the slow/cardiac muscle-specific troponin C (cTnC) enhancer contains a specific binding site for the lineage-restricted zinc finger transcription factor GATA-4. This GATA-4-binding site is required for enhancer activity in primary cardiac myocytes. Moreover, the cTnC enhancer can be transactivated by overexpression of GATA-4 in non-cardiac muscle cells such as NIH 3T3 cells. In situ hybridization studies demonstrate that GATA-4 and cTnC have overlapping patterns of expression in the hearts of postimplantation mouse embryos and that GATA-4 gene expression precedes cTnC expression. Indirect immunofluorescence reveals GATA-4 expression in cultured cardiac myocytes from neonatal rats. Taken together, these results are consistent with a model in which GATA-4 functions to direct tissue-specific gene expression during mammalian cardiac development.
机译：心肌细胞的独特收缩表型由一组心肌特异性基因的表达决定。与其他哺乳动物发育系统类似，心脏基因的协调表达可能受与这些基因的转录调控区域中的启动子和增强子元件相互作用的谱系特异性转录因子控制。尽管先前的报道已经鉴定出几种心肌特异性转录元件，但对调节这些元件的谱系特异性转录因子了解较少。在此报告中，我们证明了慢/心肌特异性肌钙蛋白C（cTnC）增强子包含谱系限制的锌指转录因子GATA-4的特异性结合位点。该GATA-4结合位点是原代心肌细胞中增强子活性所必需的。此外，cTnC增强子可通过非心脏肌肉细胞（如NIH 3T3细胞）中GATA-4的过表达而被激活。原位杂交研究表明，GATA-4和cTnC在植入后小鼠胚胎的心脏中具有重叠的表达模式，并且GATA-4基因的表达先于cTnC的表达。间接免疫荧光揭示了新生大鼠培养的心肌细胞中GATA-4的表达。两者合计，这些结果与在哺乳动物心脏发育过程中GATA-4发挥功能指导组织特异性基因表达的模型是一致的。

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