hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors.

Abstract

The myocyte enhancer-binding factor 2 (MEF2) site is an essential element of many muscle-specific enhancers and promoters that binds nuclear proteins from muscle and brain. Recently, we have cloned a family of MEF2 transcription factors produced by two genes that, at the mRNA level, are broadly expressed and produce tissue-specific isoforms by posttranscriptional processes (Y.-T. Yu, R. E. Breitbart, L. B. Smoot, Y. Lee, V. Mahdavi, and B. Nadal-Ginard, Genes Dev. 6:1783Dev. 6: -1798Dev. 6: , 1992 Diverse cellular signals are involved in the induction of cell-type-specific genes that commit multipotent precursor cell lines to specific cell lineages. During the last decade, identification of factors responsible for the commitment of cells to a particular developmental fate has been one of the most productive aspects of developmental biology. The formation of skeletal muscle has proven to be a powerful model for the study of the mechanisms involved in both the production of cellular lineages as well as the establishment of the differentiated phenotype in vertebrates. Identification of the family of basic helix-loop-helix (bHLH) myogenic regulators (the MyoD family) as factors which can induce the myogenic program in a number of mesodermally derived cells has advanced our understanding of this process. The demonstration that they function as sequence-specific transcription factors, binding at the E-box present in many muscle enhancers and promoters, has become a paradigm for the analysis of cell determination and differentiation (16,38,50). However, despite the elegance and persuasiveness of the myogenesis model based on the MyoD family, it is clear that this family of regulators can neither be the exclusive myogenic determinants nor be wholly responsible for muscle-specific gene transcription. This is so because not all muscle-specific genes contain E-boxes, and even when they are present, they are not necessarily required for musclespecific gene regulation (4-7, 9, 18, 21, 25, 31, 36, 49, 53 Several families of transcription factors, in addition to the MyoD family of regulators, which mediate lineage determination and differentiation, such as the homeodomain (13) and MADS-box proteins (52), have been found to be expressed in muscle tissue. These factors have been proven to mediate lineage determination and differentiation in other systems and could provide new insights on the molecular mechanisms of myogenesis. In particular, the known homeotic function of MADS-box proteins in plants (11,26), together with their cooperative interaction with homeodomain proteins (23, 48), identifies them as candidates for evolutionarily conserved determinants of cell lineage. These interactions reveal a molecular strategy which through combinatorial mechanisms could generate a plethora of discrete signals necessary for the specification of a large number of different cell types by a limited number of factors.Recently, a new family of MADS-box transcription factors named the myocyte enhancer factor 2 (MEF2) genes have been identifi...

ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons

“…MEF2A and MEF2C are known substrates of ERK5, and their transactivating activity can be stimulated by ERK5 via direct phosphorylation (15,17). In addition to muscle, MEF2A and MEF2C are expressed in developing and adult brain including cortex and cerebellum (43)(44)(45)(46). Our data demonstrate that BDNF regulation of MEF2C-mediated gene expression in E17 cortical neurons is ERK5-dependent.…”

Signaling by dual specificity kinases

“…Although, the functional signi®cance of this pathway in relation to other MKK-signaling pathway remains unclear, it is signi®cant to note here that p38MAPK and ERK2 can also phosphorylate and activate MEF2C. In this context, it is interesting to note that MKK5 and ERK5 are highly expressed in cardiac skeletal muscle (Zhou et al, 1995;English et al, 1995) while MEF2 family of transcription factors are mainly expressed in skeletal muscle and brain tissue (Martinet et al, 1994;McDermott et al, 1994). Taken together, these observation may be indicative of the critical role played by MKK5-ERK5 signaling pathway in cardiac physiology (Zhou et al, 1995).…”

Aberrant Extracellular Signal-Regulated Kinase (ERK) 5 Signaling in Hippocampus of Suicide Subjects

“…MEF2C is a member of the family of transcription factor MEF2 (Kato et al, 1997;Marinissen et al, 1999) and is highly expressed in developing and adult brain (Leifer et al, , 1994McDermott et al, 1993;Lyons et al, 1995). Activation of ERK5 leads to phosphorylation and therefore enhanced transactivation capacity of MEF2C (Yang et al, 1998).…”