An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133

被引:345
作者
Liu, Ning [1 ]
Williams, Andrew H. [1 ]
Kim, Yuri [1 ]
McAnally, John [1 ]
Bezprozvannaya, Svetlana [1 ]
Sutherland, Lillian B. [1 ]
Richardson, James A. [2 ]
Bassel-Duby, Rhonda [1 ]
Olson, Eric N. [1 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA
关键词
striated muscle; heart development; transcriptional regulation;
D O I
10.1073/pnas.0710558105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:20844 / 20849
页数:6
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