Mef2

Myocyte Enhancer Factor-2 (MEF2) is a transcription factor or family of transcription factors that contain both the MADS-box and MEF2 DNA-binding domains. Many, if not all, members of the MEF2 family are required for proper development of an embryo.

MEF2 was originally identified as a transcription factor in Drosophila (sometimes called D-MEF2) through promoter analysis of the muscle creatine kinase (mck) gene to identify nuclear factors interacting with the mck enhancer region.

While Drosophila has the single MEF2 gene, Vertebrates have four versions of the Mef2 gene (Mef2a, Mef2b, Mef2c, and Mef2d), all expressed in distinct but overlapping patterns during embryogenesis through adulthood. All of the mammalian Mef2 genes share approximately 50% overall amino acid identity and about 95% similarity throughout the highly conserved N-terminal MADS-box and MEF2 domains, however their sequences diverge in their C-terminal transactivation domain. The MADS-box serves as the minimal DNA-binding domain, however an adjacent 29-amino acid extension called the MEF2 domain is required for high affinity DNA-binding and dimerization. Through an interaction with the MADS-box, MEF2 transcription factors have the ability to homo- and heterodimerize, and a classic nuclear localization sequence (NLS) in the C-terminus of MEF2A, -C, and – D ensures nuclear localization of the protein. Interestingly, D-MEF2 and MEF2B lack this conserved NLS but are still found in the nucleus.