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FLASH GENE
Symbol MEF2A contributors: mct/ - updated : 22-06-2017
HGNC name myocyte enhancer factor 2A
HGNC id 6993
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a MADS(yeast Mcm1, plant homeotic Agamous and Deficiens human Serum response factor) domain at the N terminus mediating dimerization and DNA binding
  • immediatly followed by a MEF2 specific domain and forming with it a DNA binding and dimerization domains
  • a C terminus required for transcription activation and nuclear localization
    • HOMOLOGY
    intraspecies paralog to MEF2B
    Homologene
    FAMILY
  • MEF2 family
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • associating with HDAC4, HDAC in regulation of skeletal myogenesis
  • may be playing an important role in controlling vascular morphogenesis and muscle differentiation and development
  • mediating calcium-dependent transcription of the interleukin-2 gene in T lymphocytes
  • implicated in neuronal activity-dependent cell survival, and may be regulate excitatory synapse number and postsynaptic differentiation of dendrites
  • implicated in the regulation of adult bone mass
  • playing a role as an intermediary in coordinating respiratory chain subunit expression in heart and muscle through a NRF1 --> MEF2A --> COX(H) transcriptional cascade
  • with MITF function cooperatively with NFATC1 to transactivate the ATP6V0D2 promoter during RANKL-induced osteoclastogenesis
  • important component in GNA13-mediated angiogenesis
  • possible dual roles of MEF2A and MEF2D in macrophages, as activators or as repressors of gene transcription
  • additional role in maintenance of mitochondrial health, a role that may also be shared by other mitochondrial protein synthesis factors
  • role in cardiomyocyte survival through regulation of costamere integrity
  • indispensable for costamere/focal adhesion integrity and survival of cardiac muscle cells
  • nodal point in the reception and interpretation of mechanical signals to promote cytoarchitectural remodeling in cardiomyocytes
  • MIR155-mediated repression of MEF2A plays a role in the regulation of muscle gene expression
  • key role of MEF2C isoform in the brain, suggesting that MEF2A and MEF2D have only subtle roles in regulating hippocampal synaptic function (
  • contrary to skeletal muscle development, MEF2A is required for adult myogenesis in response to injury
  • essential role for MEF2A in skeletal muscle regeneration
  • distinct roles for MEF2A, PCDH10 and FMR1 in regulated degradation of DLG4 and synapse elimination, suggesting a common deficit in activity-dependent synapse elimination among different genetic causes of autism
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • BMP2 and MEF2A are key components of a pathway that controls the cardiac ventricular contractility
  • MEF2A-XIRP2 pathway that functions downstream of AGT signaling to modulate its pathological effects in the heart
    • a component
  • PIAS2-MEF2A sumoylation signaling link as a key mechanism that orchestrates postsynaptic dendritic claw morphogenesis in the cerebellar cortex and may have novel functions for SUMO E3 ligases in brain development and plasticity
  • MEF2A/MEF2D dimers strongly interact with HDAC1, and to a lesser extent with HDAC7 in macrophages, whereas low levels of MEF2A/MEF2D–HDAC1 complexes are found in undifferentiated cells or in monocytes
    • INTERACTION
    DNA binding to myocyte-specific enhancer
    RNA
    small molecule
    protein
  • interacting with TWIST to inhibit myogenesis
  • interacting with members of the MyoD family of transcriptional activator and with GATA-binding protein, and histone deacetylase
  • SLC2A4 and SLC2A4RG (to activate SLC2A4 transcription)
  • interacting with NFATC2
  • binding SUV39H1 and CABIN1 (targeting its promoter in a calcium-dependent manner)
  • interacting with XIRP2
  • MEF2C is direct transcriptional target of SOX10 and MEF2A via a evolutionarily conserved enhancer
  • XIRP2 and CMYA5 are MEF2A-dependent genes that encode costamere-localized proteins
  • MIR155 is an important regulator of MEF2A expression, having a function in muscle gene expression and myogenic differentiation
  • repression of MEF2A activity by PRKACA-dependent proteolysis of HDAC4
  • molecular interplay of NR3C1 and MEF2A in the control of genes important for neuronal plasticity
  • MEF2A directly regulates the MEG3-DIO3 cluster from the MEG3 proximal promoter region
  • MEF2A and FMR1 cooperatively regulate the expression of PCDH10
  • PCDH10 is required for MEF2A-induced synapse elimination and functions to deliver ubiquitinated DLG4, a critical synaptic scaffolding molecule to the proteasome
  • essential and redundant roles of MEF2A, MEF2C, and MEF2D in satellite cell differentiation
  • transcription factor MEF2A and PLAGL1 mediate MIF-induced SLC2A4 expression through CD74-dependent AMPK activation in cardiomyocytes
  • AKAP6 promotes MYOG expression through myocyte enhancer factor 2A (MEF2A)
  • MEF2A and JUN confer antagonistic regulation of HSPB7 gene expression in skeletal muscle, with implications for autophagy and muscle atrophy )
    • cell & other
    REGULATION
    activated by can be activated by BMP2 signaling in neonatal cardiomyocytes
    repressed by HDAC4 through multiple independent repressive domains
    MIR155, that is one of the primary miRNAs that significantly represses the expression of MEF2A
    Other negatively regulated by MITR in association with HDAC1
    regulated by PIAS1 (nuclear E3 ligase, PIAS1, promotes sumoylation of MEF2A, and protein sumoylation could play a pivotal role in controlling MEF2 transcriptional activity)
    sumoylation of MEF2A promotes the differentiation of postsynaptic granule neuron dendritic claws in the cerebellar cortex
    ASSOCIATED DISORDERS
    corresponding disease(s) ADCAD1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    having an impact on histone hyperacetylation in hepatocellular carcinoma
    constitutional     --low  
    of endogenous GNA13 and MEF2 proteins in endothelial cells reduced cell proliferation and capillary tube formation
    Susceptibility to myocardial infarction
    Variant & Polymorphism SNP P279L risk factor for myocardial infarction
    Candidate gene for congenital diaphragmatic hernia
    Marker
    Therapy target BMP2-MEF2A pathway can offer new opportunities for the treatment of heart failure
    ANIMAL & CELL MODELS