title: A Mef2 gene that generates a muscle-specific isoform via alternative mRNA splicing.
abstract: Members of the myocyte-specific enhancer-binding factor 2 (MEF2) family of transcription factors bind a conserved A/T-rich sequence in the control regions of numerous muscle-specific genes. Mammalian MEF2 proteins have been shown previously to be encoded by three genes, Mef2, xMef2, and Mef2c, each of which gives rise to multiple alternatively spliced transcripts. We describe the cloning of a new member of the MEF2 family from mice, termed MEF2D, which shares extensive homology with other MEF2 proteins but is the product of a separate gene. MEF2D binds to and activates transcription through the MEF2 site and forms heterodimers with other members of the MEF2 family. Deletion mutations show that the carboxyl terminus of MEF2D is required for efficient transactivation. MEF2D transcripts are widely expressed, but alternative splicing of MEF2D transcripts gives rise to a muscle-specific isoform which is induced during myoblast differentiation. The mouse Mef2, Mef2c, and Mef2d genes map to chromosomes 7, 13, and 3, respectively. The complexity of the MEF2 family of regulatory proteins provides the potential for fine-tuning of transcriptional responses as a consequence of combinatorial interactions among multiple MEF2 isoforms encoded by the four Mef2 genes.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
authors.forename: J F
authors.initials: JF
authors.lastname: Martin
authors.forename: J M
authors.initials: JM
authors.lastname: Miano
authors.forename: C M
authors.initials: CM
authors.lastname: Hustad
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: E N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D064326:MEF2 Transcription Factors; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D046911:Macromolecular Substances; C578041:Mef2c protein, mouse; C578044:Mef2d protein, mouse; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D014157:Transcription Factors