Disease relevance of Mef2

• These results support earlier reports that DlEPV is a member of the sub-family Entomopoxvirinae, most likely in Group C, and is the first symbiotic EPV described to date from a parasitic wasp [1].

Psychiatry related information on Mef2

• Evidence is now accumulating that many of the co-factors (E12, Id, MEF2 and CRP proteins) that regulate MRF activity in mammals are also present in lower vertebrates [2].

High impact information on Mef2

• Members of the myocyte enhancer binding factor-2 (MEF2) family of MADS (MCM1, agamous, deficiens, and serum response factor) box transcription factors are expressed in the skeletal, cardiac, and smooth muscle lineages of vertebrate and Drosophila embryos [3].
• The expression of DmiR-1 is controlled by the Twist and Mef2 transcription factors [4].
• Twist protein can bind to this E box to activate Mef2 transcription, and ectopic expression of twist results in ectopic activation of the wild-type 175-bp enhancer [5].
• The myogenic regulatory gene Mef2 is a direct target for transcriptional activation by Twist during Drosophila myogenesis [5].
• These findings define a novel transcriptional pathway required for skeletal muscle development and identify Twist as an essential and direct regulator of Mef2 expression in the somatic mesoderm [5].

Biological context of Mef2

• Results from an independent molecular screen for binding factors to a myoblast-specific Mef2 enhancer further demonstrate that Lmd is a direct transcriptional regulator of Mef2 in fusion-competent myoblasts [6].
• Drosophila MEF2, a transcription factor that is essential for myogenesis [7].
• We have characterized genetic deficiencies and EMS-induced point mutations that result in complete loss of MEF2 protein in homozygous mutant embryos [7].
• This fragment contained a MEF2 binding site conserved between D. melanogaster and Drosophila virilis which bound MEF2 protein in embryo nuclear extracts [8].
• D-mef2 gene expression is first detected during Drosophila embryogenesis within mesodermal precursor cells prior to specification of the somatic and visceral muscle lineages [9].

Anatomical context of Mef2

• These findings underscore the importance of regulated Lmd protein activity in maintaining proper activation of downstream target genes, such as Mef2, within fusion-competent myoblasts [10].
• Embryos that lack lmd function show a loss of expression of two key differentiation and fusion genes, Mef2 and sticks-and-stones, in fusion-competent myoblasts and are completely devoid of multinucleate muscle fibers [6].
• Here we describe a complex enhancer located 5.8 kb upstream of the Drosophila Mef2 gene that controls transcription in cardial cells of the dorsal vessel, a subset of somatic muscle founder cells, and the visceral muscle cells [11].
• We show herein that the Drosophila MEF2 protein is expressed throughout the mesoderm following gastrulation [7].
• Histological analysis of these animals revealed a requirement for MEF2 in skeletal muscle patterning, although these animals had strikingly normal amounts of muscle tissue [12].

Associations of Mef2 with chemical compounds

• Mutant embryos also exhibit an abnormal midgut morphology, which correlates with the absence of alpha PS2 integrin gene expression and muscle-specific enhancer function, suggesting that D-mef2 regulates the inflated locus which encodes this integrin subunit [13].

Regulatory relationships of Mef2

• Dmeso18E expression is regulated by Dmef2, although some expression is Dmef2-independent [14].
• Here, we show that the bHLH transcription factor Twist directly regulates Mef2 expression in adult somatic muscle precursor cells via a 175-bp enhancer located 2245 bp upstream of the transcriptional start site [5].
• Furthermore, we showed that these factors and, in addition, Dmef2 are able to ectopically activate rst expression via the previously described rst cis-regulatory modules [15].
• The muscleblind gene participates in the organization of Z-bands and epidermal attachments of Drosophila muscles and is regulated by Dmef2 [16].
• Myocyte-specific enhancer factor 2 acts cooperatively with a muscle activator region to regulate Drosophila tropomyosin gene muscle expression [17].

Other interactions of Mef2

• Transcription of the myogenic regulatory gene Mef2 in cardiac, somatic, and visceral muscle cell lineages is regulated by a Tinman-dependent core enhancer [11].
• Novel enhancers for D-mef2 transcription in cardiac and adult muscle precursor cells have been identified and their regulation by the Tinman and Twist myogenic factors have been demonstrated [18].
• Single-minded, Dmef2, Pointed, and Su(H) act on identified regulatory sequences of the roughest gene in Drosophila melanogaster [15].
• D-mef expression is not dependent on the function of tin, and embryos that are deficient for the mesodermal gene DFR1 also show normal initiation of D-mef2 expression at blastoderm [19].
• In addition, fusion-competent myoblasts fail to express proteins characteristic of the general pathway of myogenesis such as myosin and Dmef2 [20].

Analytical, diagnostic and therapeutic context of Mef2

• Using quantitative polymerase chain reaction, we determined that expression of the MEF2-regulated actin gene Act57B was severely reduced in these animals [12].
• To understand how these transcription factors control diverse processes in muscle development, we have combined chromatin immunoprecipitation analysis with gene expression profiling to obtain a temporal map of Mef2 activity during Drosophila embryonic development [21].
• Full-length RT-PCR products for nautilus and DMEF2 encode immunoprecipitable proteins [22].
• We propose that these cis-elements and the proteins that they bind regulate muscle activator function and together with MEF2 are capable of regulating high level muscle expression [23].

References