Table 1. Expression, transcriptional activity and associated diseases of MEF-2 isoforms.
| Isoforms | Expression | Development | Mutations | Activity | Gene-targets | Disease |
|---|---|---|---|---|---|---|
| MEF-2A | Expressed in brain, endocrine tissue, lung, skin and soft tissue. Expressed in cardiac, skeletal and smooth muscle. Highly overexpressed in glioma, lymphoma, and melanoma. |
Required for proliferation, differentiation and maturation of neural stem cells into neurons and glial cells [164, 165]. Muscle-regeneration and tissue repair [95]. Myofibroblast differentiation [158]. |
MEF-2A mutations is associated with premature myocardial infarction and coronary heart disease [172]. Also associated with reduced myofibroblast proliferation and differentiation [152]. |
Downregulation of Wnt signaling via miRNA/Gtl2-Dio3 loci [155]. Regulates miRNA-143 [156]. Regulates Calpain 3 gene expression [95]. Also, involved in immune response [180, 183, 184]. |
MEF-2A is located on chromosome 15q26 [154]. GSK3beta and Xirp2 are transcriptional target of MEF-2A [53–55, 161]. Cited2 is a possible transcriptional target [155]. |
MEF-2A is involved in the pathogenesis of HTLV-1 and ATLL [18, 26–40]. Accelerates the progression of atherosclerosis [184]. Implicated in HCC and gastric cancer [180, 183]. |
| MEF-2B | Expressed in tonsil, appendix, germinal center of lymph node, and bone marrow. Highly-expressed in lung carcinoma and lymphoma. Expressed in cardiac and skeletal muscle. |
MEF-2B is required for the development of cardiac and skeletal muscle [189]. | Mutation causes dysregulation of proto-oncogene BCL6 [193, 194]. Associated with leukemia and carcinoma [193, 195–197]. |
Promotes tumorigenesis [125]. |
MEF-2B is located on chromosome 19p12 [154]. ROS-induced NOX-1 signaling [188]. Binds in the promoter of DDAIS [125]. |
Involved in follicular lymphoma, Burkitt's lymphoma, mantle cell lymphoma, splenic marginal zone lymphoma, and diffuse large B cell lymphoma [196, 197]. Hypertension in VSMCs [188] and TGFβ-induced EMT and tumorigenesis [125, 191]. |
| MEF-2C | Expressed in nucleoplasm and neuroplasmic vesicles. Expressed in cardiac, skeletal muscle and brain tissue (especially in cortical excitatory neurons). Expressed in both common myeloid & lymphoid progenitors. Maturing hematopoietic stem cells and B cells. |
It is involved in the development of cardiac and skeletal muscle [152]. Development of lymphoid and myeloid progenitor cells [153]. Development of the cerebrocortex in its role in corticostriatal circuit [202]. |
Associated with decline in cognitive ability as well as in development of autism, schizophrenia, and epilepsy [10, 202–204]. Implicated in congenital heart defect and forelimb malformations [210, 221]. |
It possesses differential activity in membrane depolarization [201]. Required for neuronal differentiation and commitment of embryonic stem cells [199]. |
MEF-2C is located on chromosome 5q14 [154]. Target genes include GPM6A, DLx6, Hand2, Myogenin, and Myokinase [200, 207, 233]. |
MEF-2C implicated in DiGeorge syndrome [209]. |
| MEF-2D | Highly expressed in cerebrocortex, endocrine system, skin, kidney, and breast. Present in hematopoietic stem cells and germinal centers of lymph node. Expressed in cardiac and skeletal muscles. |
It is required for the development of neuronal and muscle cells [53, 54]. Terminal differentiation of neonatal cardiomyocytes and human macrophages [163, 52]. |
Mutation implicated in the inhibited differentiation of common lymphoid progenitors (differentiation into CD19 positive B-cells) [248]. | Promotes the survival of dopaminergic neurons [242]. In GLUT-4 transcriptional activity [158, 182]. |
MEF-2D is located on chromosome 1q12-q23 [154]. DYRK1A is a target gene [240]. |
MEF-2D is involved in cancer of the colorectal tissue, breast, prostate, lung, liver, and thyroid [124, 125]. Implicated in melanoma [279–281], and pathobiology of B-cell acute lymphoblastic leukemia (B-ALL) [248]. Also, Parkinson's disease, cardiac myxoma, and lung cancer [239, 244, 250, 251]. |