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

Ning Liu, Andrew H. Williams, Yuri Kim, John McAnally, Svetlana Bezprozvannaya, Lillian B. Sutherland, James A. Richardson, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticle

325 Scopus citations

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 musclespecific 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.

Original languageEnglish (US)
Pages (from-to)20844-20849
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number52
DOIs
StatePublished - Dec 26 2007

Keywords

  • Heart development
  • Striated muscle
  • Transcriptional regulation

ASJC Scopus subject areas

  • General

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