An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133
An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133
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DOI：
10.1073/pnas.0710558105
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发表时间：
2007-12-26
影响因子：
11.1
通讯作者：
Olson, Eric N.
中科院分区：
文献类型：
--
作者：
Liu, Ning;Williams, Andrew H.;Olson, Eric N.
肌肉特异性microRNA，miR-1和miR-133，在肌肉生长和分化中起重要作用。在这里，我们表明，MEF 2转录因子，肌肉发育的重要调节因子，直接激活双顺反子初级转录本编码的miR-1-2和133 a-1通过基因内肌肉特异性增强子之间的miR-1 -2和133 a-1编码区的转录。这种MEF 2依赖性增强子在小鼠胚胎发育期间在线性心管中被激活，此后控制心脏的整个心房和心室腔的转录。MEF 2与MyoD一起还调节胚胎发生和成年期间体节肌节和所有骨骼肌纤维中的miR-1-2/133 a-1基因内增强子。类似的肌肉特异性基因内增强子控制miR-1-1/-133a-2基因座的转录。这些发现揭示了与miR-1/-133基因相关的调控元件的共同结构，并强调了MEF 2作为控制心脏和骨骼肌发育的转录和转录后途径的调控因子的核心作用。
The muscle-specific microRNAs, miR-1 and miR-133, play important roles in muscle growth and differentiation. Here, we show that the MEF2 transcription factor, an essential regulator of muscle development, directly activates transcription of a bicistronic primary transcript encoding miR-1-2 and 133a-1 via an intragenic muscle-specific enhancer located between the miR-1-2 and 133a-1 coding regions. This MEF2-dependent enhancer is activated in the linear heart tube during mouse embryogenesis and thereafter controls transcription throughout the atrial and ventricular chambers of the heart. MEF2 together with MyoD also regulates the miR-1-2/133a-1 intragenic enhancer in the somite myotomes and in all skeletal muscle fibers during embryogenesis and adulthood. A similar muscle-specific intragenic enhancer controls transcription of the miR-1-1/-133a-2 locus. These findings reveal a common architecture of regulatory elements associated with the miR-1/-133 genes and underscore the central role of MEF2 as a regulator of the transcriptional and posttranscriptional pathways that control cardiac and skeletal muscle development.