Gene Section Mini Review Atlas Genet Cytogenet Oncol Haematol. 2010; 14(8) 772 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS MEF2D (myocyte enhancer factor 2D) Victor Prima, Lyudmyla G Glushakova, Stephen P Hunger University of Florida College of Medicine, Gainesville, FL 32610, USA (VP, LGG); Children's Hospital and the Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA (SPH) Published in Atlas Database: October 2009 Online updated version : http://AtlasGeneticsOncology.org/Genes/MEF2DID43636ch1q22.html DOI: 10.4267/2042/44827 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Other names: DKFZp686I1536 HGNC (Hugo): MEF2D Location: 1q22 Note: MEF2D is a member of the family of myocyte enhancer factor MEF2 that includes MEF2A, MEF2B, MEF2D, MEF2C. DNA/RNA Description 12 exons. Transcription 5888 bp mRNA, coding sequence: from 391 bp to 1956 bp (NCBI, GenBank NM_005920); alternative splicing in E3 (3alpha1 and 3alpha2) and beta produces 4 splicing isoforms: alpha1, alpha1beta, alpha2, alpha2beta (Zhu et al., 2005). Protein Note MEF2D belongs to MEF2 (myocyte enhancer factor 2)- like/Type II subfamily of MADS (MCM1, Agamous, Deficiens, and SRF (serum response factor) box family of eukaryotic transcriptional regulators). Description MEF2D encodes approximately a 521 aa-long protein (GenBank at NCBI presented 4 isoforms: CRA_a, 521 aa, EAW52952.1; CRA_b, 143 aa, EAW52949.1; CRA_c, 288 aa, EAW52950.1; CRA_d, 523 aa, EAW52951.1). It is composed of several domains: the MADS-box on N terminus (2-78 aa, MAD MEF2 like); the 29-aa MEF2 domain immediately C-terminal to the MADS- box (unique to the MEF2 factors); C-terminal transcriptional activation domains. Both MADS and MEF2 domains are necessary and sufficient for dimerization and binding to the DNA sequence CTA(A/T) 4 TAG/A. MEF2 domain influences cofactor interactions (Pollock and Treisman, 1991; Molkentin and Olson, 1996). Regions: 2-38 aa of the MADS domain confer DNA binding site specificity; 21-73 aa, dimerization interface; 59 aa, putative phosphorylation site. Expression High level expression in muscles and neurons, at lower levels in a wide range of cell types (Black and Olson, 1998). Localisation Nuclear (Neely et al., 2009). Function DNA binding, transcriptional activation. Transmission of extracellular signals to the genome, control of cell differentiation, proliferation, morphogenesis, survival and apoptosis of a wide range of cell types. Important in immediate-early development in animals. MEF2D dimers regulate expression of genes involved in muscle-specific and/or growth factor-related transcription. It seems to be transcriptional effector of mitogenic signaling pathways initiated by mitogen-activated protein kinases (MAPKs) including p38 and ERK5 (extracellular signal-related kinase 5)/Big MAPK-1, and also plays critical roles in calcium-regulated