Mas José-Antonio, García-Zaragoza Elena, Cervera Margarita
Departamento de Bioquímica and Instituto de Investigaciones Biomédicas, Facultad de Medicina, Universidad Autonoma de Madrid, UAM-CSIC, 28029 Madrid, Spain.
Mol Biol Cell. 2004 Apr;15(4):1931-45. doi: 10.1091/mbc.e03-10-0729. Epub 2004 Jan 12.
The control of muscle-specific expression is one of the principal mechanisms by which diversity is generated among muscle types. In an attempt to elucidate the regulatory mechanisms that control fiber diversity in any given muscle, we have focused our attention on the transcriptional regulation of the Drosophila Troponin T gene. Two, nonredundant, functionally identical, enhancer-like elements activate Troponin T transcription independently in all major muscles of the embryo and larvae as well as in adult somatic and visceral muscles. Here, we propose that the differential but concerted interaction of these two elements underlies the mechanism by which a particular muscle-type establish the correct levels of Troponin T expression, adapting these levels to their specific needs. This mechanism is not exclusive to the Troponin T gene, but is also relevant to the muscle-specific Troponin I gene. In conjunction with in vivo transgenic studies, an in silico analysis of the Troponin T enhancer-like sequences revealed that both these elements are organized in a modular manner. Extending this analysis to the Troponin I and Tropomyosin regulatory elements, the two other components of the muscle-regulatory complex, we have discovered a similar modular organization of phylogenetically conserved domains.
肌肉特异性表达的控制是在不同肌肉类型之间产生多样性的主要机制之一。为了阐明控制任何特定肌肉中纤维多样性的调控机制，我们将注意力集中在果蝇肌钙蛋白T基因的转录调控上。两个非冗余、功能相同的增强子样元件在胚胎和幼虫的所有主要肌肉以及成虫的体壁和内脏肌肉中独立激活肌钙蛋白T的转录。在此，我们提出这两个元件的差异但协同的相互作用是特定肌肉类型建立正确水平的肌钙蛋白T表达并使其水平适应其特定需求的机制基础。这种机制并非肌钙蛋白T基因所特有，对肌肉特异性肌钙蛋白I基因也同样适用。结合体内转基因研究，对肌钙蛋白T增强子样序列的计算机分析表明，这两个元件均以模块化方式组织。将此分析扩展至肌肉调节复合体的另外两个组成部分——肌钙蛋白I和原肌球蛋白调控元件，我们发现了系统发育保守结构域的类似模块化组织。
