Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
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Contributed by Eric N. Olson, November 7, 2007 (received for review October 17, 2007)
Abstract
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.
Footnotes
- ‡To whom correspondence should be addressed. E-mail: eric.olson{at}utsouthwestern.edu
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Author contributions: N.L., R.B.-D., and E.N.O. designed research; N.L., A.H.W., Y.K., S.B., and L.B.S. performed research; A.W. and J.M. contributed new reagents/analytic tools; N.L., J.A.R., R.B.-D., and E.N.O. analyzed data; and N.L. and E.N.O. wrote the paper.
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The authors declare no conflict of interest.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0710558105/DC1.
- © 2007 by The National Academy of Sciences of the USA
An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133
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