TheMef2cgene is a direct transcriptional target of myogenic bHLH and MEF2 proteins during skeletal muscle development

Citations Over TimeTop 16% of 2001 papers

Abstract

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.

Related Papers

• → Mef2 gene expression marks the cardiac and skeletal muscle lineages during mouse embryogenesis(1994)569 cited
• → Regulation of Skeletal Muscle Sarcomere Integrity and Postnatal Muscle Function by Mef2c(2007)216 cited
• → Nitric oxide drives embryonic myogenesis in chicken through the upregulation of myogenic differentiation factors(2013)51 cited
• → The molecular characterization and temporal–spatial expression of myocyte enhancer factor 2 genes in the goat and their association with myofiber traits(2014)19 cited
• → The Mouse MRF4 Promoter Is trans-Activated Directly and Indirectly by Muscle-specific Transcription Factors(1995)89 cited