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Development 128, 4623-4633 (2001)
© 2001 The Company of Biologists Limited

The Mef2c gene is a direct transcriptional target of myogenic bHLH and MEF2 proteins during skeletal muscle development

Da-Zhi Wang1,*, M. Renee Valdez1,*, John McAnally1, James Richardson1,2 and Eric N. Olson1,{ddagger}

1 Department of Molecular Biology,
2 Department of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9148, USA
* These authors contributed equally to this work

{ddagger}Author for correspondence (e-mail: eolson{at}hamon.swmed.edu)

Accepted August 20, 2001

Members of the MEF2 family of transcription factors are upregulated during skeletal muscle differentiation and cooperate with the MyoD family of myogenic basic helix-loop-helix (bHLH) transcription factors to control the expression of muscle-specific genes. To determine the mechanisms that regulate MEF2 gene expression during skeletal muscle development, we analyzed the mouse Mef2c gene for cis-regulatory elements that direct expression in the skeletal muscle lineage in vivo. We describe a skeletal muscle-specific control region for Mef2c that is sufficient to direct lacZ reporter gene expression in a pattern that recapitulates that of the endogenous Mef2c gene in skeletal muscle during pre- and postnatal development. This control region is a direct target for the binding of myogenic bHLH and MEF2 proteins. Mutagenesis of the Mef2c control region shows that a binding site for myogenic bHLH proteins is essential for expression at all stages of skeletal muscle development, whereas an adjacent MEF2 binding site is required for maintenance but not for initiation of Mef2c transcription. Our findings reveal the existence of a regulatory circuit between these two classes of transcription factors that induces, amplifies and maintains their expression during skeletal muscle development.

Key words: Skeletal muscle, MEF2C, Mouse, bHLH, MEF2, Myogenesis




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© The Company of Biologists Ltd 2001