MEF2

MEF2, short for myocyte enhancer factor 2, is a family of transcription factors belonging to the MADS-box superfamily. In mammals, four MEF2 genes—MEF2A, MEF2B, MEF2C, and MEF2D—encode related proteins that regulate gene expression during muscle differentiation and development, and also contribute to neural development and function.

MEF2 proteins contain a conserved MADS-box DNA-binding domain and a MEF2 domain that mediates dimerization and DNA recognition. They bind as homo- or heterodimers to MEF2 response elements in target genes, coordinating transcriptional programs required for cell fate specification in muscle and other tissues.

Regulation of MEF2 activity involves multiple signaling pathways. Calcium/calcineurin signaling promotes MEF2 activation, while mitogen-activated protein kinase pathways can modulate its activity through phosphorylation. Class II histone deacetylases (HDAC4, HDAC5, HDAC7, HDAC9) repress MEF2 by direct interaction; signals that cause HDACs to export from the nucleus relieve repression. Coactivators such as p300/CBP can enhance MEF2-dependent transcription by promoting histone acetylation and chromatin accessibility.

Biological roles of MEF2 span muscle and brain. In skeletal and cardiac muscle, MEF2 drives differentiation, influences fiber-type specification, and contributes to cardiac morphogenesis and hypertrophy. In the nervous system, MEF2 factors participate in neuronal differentiation, synaptic development, and activity-dependent plasticity, affecting learning and memory processes.

Expression of MEF2 genes is broad but enriched in muscle and brain. Mouse genetic studies show essential roles in muscle formation and heart development, and dysregulation of MEF2 activity has been linked to developmental, muscular, and cardiac diseases. See also MADS-box transcription factors and myogenesis.