Regional Chromosomal Assignments for Four Members of the MADS Domain Transcription Enhancer Factor 2 (MEF2) Gene Family to Human Chromosomes 15q26, 19p12, 5q14, and 1q12–q23

Lawrence Livermore National Laboratory, Livermore, California, United States
Genomics (Impact Factor: 2.28). 11/1995; 29(3):704-11. DOI: 10.1006/geno.1995.9007
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The MEF2 genes belong to the MADS box family of transcription factors and encode proteins that bind as homo- and heterodimers to a consensus CTA(T/A)4TAG/A sequence, which is present in the regulatory regions of numerous muscle-specific and growth-inducible genes. Sequence analysis of human MEF2 cDNA clones suggests that they arose from alternatively spliced transcripts of four different genes, termed MEF2A-D. We have mapped the MEF2 genes to human chromosomal regions by identifying unique sequences in the MEF2 cDNA clones and using these sequences as PCR primers on the DNA of human-rodent hybrid clone panels that are informative for different regions of the human genome. PCR primers were also used to identify individual YAC clones for two of the genes, MEF2A and MEF2C, and a PCR product was used to identify cosmid clones for MEF2B. Genetic and physical mapping information available from genome databases on markers contained within YAC and cosmid clones provided independent assignments for those genes. Inter-Alu PCR painting probes of YAC clones were used as probes for high-resolution chromosomal regional assignment by fluorescence in situ hybridization. The localization of MEF2A to chromosome 15q26, MEF2B to 19p12, MEF2C to 5q14, and MEF2D to 1q12-q23 verifies the existence of at least four distinct loci for members of this gene family.

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Available from: Ralf Krahe, Oct 03, 2015
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    • "In vertebrates, there are four mef2 genes, referred to as mef2a, -b, -c, and -d, that are located on different chromosomes (Pollock & Treisman 1991, Yu et al 1992, Breitbart et al 1993, Leifer et al 1993, Martin et al 1993, 1994, McDermott et al 1993, Hidaka et al 1995, Hobson et al 1995, Ticho et al 1996, Molkentin et al 1996b, Suzuki et al 1996, Morisaki et al 1997). There is a single mef2 gene in each of the genomes of Drosophila (Lilly et al 1994, Nguyen et al 1994), Caenorhabditis elegans (M Krause, personal communication), and sea urchins (J Venuti, personal communication). "
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    ABSTRACT: Metazoans contain multiple types of muscle cells that share several common properties, including contractility, excitability, and expression of overlapping sets of muscle structural genes that mediate these functions. Recent biochemical and genetic studies have demonstrated that members of the myocyte enhancer factor-2 (MEF2) family of MADS (MCM1, agamous, deficiens, serum response factor)-box transcription factors play multiple roles in muscle cells to control myogenesis and morphogenesis. Like other MADS-box proteins, MEF2 proteins act combinatorially through protein-protein interactions with other transcription factors to control specific sets of target genes. Genetic studies in Drosophila have also begun to reveal the upstream elements of myogenic regulatory hierarchies that control MEF2 expression during development of skeletal, cardiac, and visceral muscle lineages. Paradoxically, MEF2 factors also regulate cell proliferation by functioning as endpoints for a variety of growth factor-regulated intracellular signaling pathways that are antagonistic to muscle differentiation. We discuss the diverse functions of this family of transcription factors, the ways in which they are regulated, and their mechanisms of action.
    Annual Review of Cell and Developmental Biology 02/1998; 14(1):167-96. DOI:10.1146/annurev.cellbio.14.1.167 · 16.66 Impact Factor
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    ABSTRACT: There are four members of the myocyte enhancer binding factor 2 (MEF2) family of transcription factors, MEF2A, -B, -C, and -D, that have homology within an amino-terminal MADS box and an adjacent MEF2 domain that together mediate dimerization and DNA binding. MEF2A, -C, and -D have previously been shown to bind an A/T-rich DNA sequence in the control regions of numerous muscle-specific genes, whereas MEF2B was reported to be unable to bind this sequence unless the carboxyl terminus was deleted. To further define the functions of MEF2B, we analyzed its DNA binding and transcriptional activities. In contrast to previous studies, our results show that MEF2B binds the same DNA sequence as other members of the MEF2 family and acts as a strong transactivator through that sequence. Transcriptional activation by MEF2B is dependent on the carboxyl terminus, which contains two conserved sequence motifs found in all vertebrate MEF2 factors. During mouse embryogenesis, MEF2B transcripts are expressed in the developing cardiac and skeletal muscle lineages in a temporospatial pattern distinct from but overlapping with those of the other Mef2 genes. The mouse Mef2b gene maps to chromosome 8 and is unlinked to other Mef2 genes; its intron-exon organization is similar to that of the other vertebrate Mef2 genes and the single Drosophila Mef2 gene, consistent with the notion that these different Mef2 genes evolved from a common ancestral gene.
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    ABSTRACT: The MADS-box encodes a novel type of DNA-binding domain found so far in a diverse group of transcription factors from yeast, animals, and seed plants. Here, our first aim was to evaluate the primary structure of the MADS-box. Compilation of the 107 currently available MADS-domain sequences resulted in a signature which can strictly discriminate between genes possessing or lacking a MADS-domain and allowed a classification of MADS-domain proteins into several distinct subfamilies. A comprehensive phylogenetic analysis of known eukaryotic MADS-box genes, which is the first comprising animal as well as fungal and plant homologs, showed that the vast majority of subfamily members appear on distinct subtrees of phylogenetic trees, suggesting that subfamilies represent monophyletic gene clades and providing the proposed classification scheme with a sound evolutionary basis. A reconstruction of the history of the MADS-box gene subfamilies based on the taxonomic distribution of contemporary subfamily members revealed that each subfamily comprises highly conserved putative orthologs and recent paralogs. Some subfamilies must be very old (1,000 MY or more), while others are more recent. In general, subfamily members tend to share highly similar sequences, expression patterns, and related functions. The defined species distribution, specific function, and strong evolutionary conservation of the members of most subfamilies suggest that the establishment of different subfamilies was followed by rapid fixation and was thus highly advantageous during eukaryotic evolution. These gene subfamilies may have been essential prerequisites for the establishment of several complex eukaryotic body structures, such as muscles in animals and certain reproductive structures in higher plants, and of some signal transduction pathways. Phylogenetic trees indicate that after establishment of different subfamilies, additional gene duplications led to a further increase in the number of MADS-box genes. However, several molecular mechanisms of MADS-box gene diversification were used to a quite different extent during animal and plant evolution. Known plant MADS-domain sequences diverged much faster than those of animals, and gene duplication and sequence diversification were extensively used for the creation of new genes during plant evolution, resulting in a relatively large number of interacting genes. In contrast, the available data on animal genes suggest that increase in gene number was only moderate in the lineage leading to mammals, but in the case of MEF2-like gene products, heterodimerization between different splice variants may have increased the combinatorial possibilities of interactions considerably. These observations demonstrate that in metazoan and plant evolution, increased combinatorial possibilities of MADS-box gene product interactions correlated with the evolution of increasingly complex body plans.
    Journal of Molecular Evolution 10/1996; 43(5):484-516. DOI:10.1007/BF02337521 · 1.68 Impact Factor
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