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MEF2B

Official Full Name
myocyte enhancer factor 2b
Synonyms
MEF2B; myocyte enhancer factor 2B; myocyte-specific enhancer factor 2B; RSRFR2; serum response factor-like protein 2; MADS box transcription enhancer factor 2, polypeptide B (myocyte enhancer factor 2B); FLJ32648; si:ch211-125m10.1

Myocyte enhancer factor 2B (MEF2B) belongs to members of the MEF2 transcription factor family, and other MEF2 proteins include MEF2A, MEF2C and MEF2D. The MEF2 protein has been found to play an important role in activating gene programs, involved in the regulation of the development of muscle cells, neural ridges, endothelial cells, chondrocytes, neurons and lymphocytes. MEF2 participates in epigenetic regulation by interacting with multiple co-activation or inhibitory factors and participates in multiple extracellular signaling pathway responses in different cell types.

MEF2B is the only gene in the family of MEF2 genes that is expressed throughout the embryonic stage and is thought to activate the target protein downstream of myofibroblastic epithelial cells. Compared with spindle cells and oval cells, the expression of MEF2B mRNA and fibroblasts in spindle cells was significantly higher than in oval cells. After knocking out the MEF2B gene in oval cells, it was found that the up-regulation of MEF2 protein, vimentin and non-calcium-modulated binding protein induced by epidermal growth factor (EGF) also disappeared, but the basic expression level of interstitial vimentin and fibronectin has been enhanced.

MEF2B Gene and Cell Differentiation

The study found that the protein complex obtained from the smooth muscle cell nuclear extract counteracts the antibody of MEF2B protein, but does not counteract the specific antibodies of MEF2A, MEF2C, MEF2D protein, suggesting that the MEF2B gene is rich in A-T. Regional binding, but MEF2B does not directly interact with A-T-rich regions. This study also demonstrated that overexpression of MEF2B in smooth muscle up-regulates the activity of the smooth muscle myosin heavy chain (SMHC) gene promoter, which is also the first to demonstrate the specific expression of the MEF2B gene in smooth muscle. Studies have found that the MEF2B gene also plays an important role in the transformation of human gingival keratinocytes.

MEF2B and Lymphoma

Studies have shown that the mRNA of MEF2B is highly expressed in B lymphocytes of germinal certer (GC), rather than naive B lymphocytes or B lymphocytes differentiated into peripheral blood. At the same time, in normal GC B lymphocytes, only MEF2B in the MEF2 protein family showed higher mRNA levels, and both transcripts of MEF2B could detect expression, and its transcription level was consistent with protooncogene B cell lymphoma 6 (B cell lymphoma 6, BCL6).

MEF2B.pngFigure 1. MEF2B acts as an oncogene in B cell lymphomagenesis. (Paola, B. , et al. 2018)

Immunohistochemical staining of 38 cases of proliferative lymphoid tissue and 471 cases of lymphoproliferative tumors revealed that MEF2B of GC B cells was strongly expressed and stained clearly in proliferative lymph nodes and lymph node invasion. The marginal zone and mononuclear B cells lacked the expression of MEF2B, and no positive expression of MFE2B was detected in the paracortex, follicular stroma and medullary lymphocytes. GC cells BCL6 antibody staining showed the same pattern, and the proportion of cells in the marginal zone and the dispersed follicles was also consistent.

MEF2B protein is highly expressed simultaneously with MEF2B mRNA in a variety of cells, whereas mRNA expression of other MEF2 is inhibited. MEF2B protein was detected in B lymphocytes, fibroblasts, myoblasts, myotubes, and vascular smooth muscle cells of GC. In 9% of ovarian cancer, 5% of uterine fibroids, 5% of adrenocortical carcinomas, and 3% of esophageal cancers, MEF2B exhibited high levels of expansion. It is suggested that MEF2B acts as an oncogene in these tumors to promote epithelial-mesenchymal transition.

References:

  1. Paola, B. , Christof, S. , Holmes, A. B. , Qiong, S. , Shafinaz, H. , & Laura, P. , et al. (2018). Mef2b instructs germinal center development and acts as an oncogene in b cell lymphomagenesis. Cancer Cell, 34(3), 453-465.e9.
  2. Xiao, L. , Haoran, S. , Yi, K. , Niroop, R. , Fang, W. , & Chandani, S. , et al. (2018). Crystal structure of apo mef2b reveals new insights in dna binding and cofactor interaction. Biochemistry, acs.biochem.8b00439-.
  3. Ying CY; Dominguez-Sola D; Fabi M; Lorenz IC; Hussein S; Bansal M; Califano A; Pasqualucci L; Basso K; Dalla-Favera R. (2013). Mef2b mutations lead to deregulated expression of the oncogene bcl6 in diffuse large b cell lymphoma. Nature Immunology, 14(10), 1084.

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