Inhibition of Myogenic bHLH and MEF2 Transcription Factors by the bHLH Protein Twist

• Published in: Science (American Association for the Advancement of Science) Vol. 272; no. 5267; pp. 1476 - 1480
• Main Authors: Spicer, Douglas B., Rhee, James, Cheung, Wang L., Lassar, Andrew B.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 07.06.1996; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors; Binding sites; Biochemistry; Biological and medical sciences; Cell Differentiation; Cell Line; Classical genetics, quantitative genetics, hybrids; COS cells; Creatine Kinase - genetics; DNA; DNA - metabolism; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drosophila; Drosophila Proteins; Fundamental and applied biological sciences. Psychology; Gene expression; Genetics of eukaryotes. Biological and molecular evolution; Helix-Loop-Helix Motifs - physiology; Individualized Instruction; Inhibition; Inhibitor of Differentiation Protein 1; Invertebrata; MEF2 Transcription Factors; Mesoderm; Mice; Muscle development; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscles; Muscular system; MyoD Protein - metabolism; MyoD Protein - physiology; Myogenesis; Myogenic Regulatory Factors; Nuclear Proteins - chemistry; Nuclear Proteins - metabolism; Nuclear Proteins - physiology; Physiological aspects; Proteins; Repressor Proteins; Skeletal muscle; TCF Transcription Factors; Transactivation; Transcription Factor 7-Like 1 Protein; Transcription factors; Transcription Factors - antagonists & inhibitors; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology; Transcriptional Activation; Transfection; Twist-Related Protein 1; Embryonic development; Insecta; Drosophila; Mesoderm; Molecular interaction; Gene expression; Myogenesis; Drosophilidae; Myogenic factor; Proteins; Regulation(control); Gene; Arthropoda; Somite; Muscle; Mutation; Invertebrata; Transcription factor; Diptera
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.272.5267.1476

The myogenic basic helix-loop-helix (bHLH) and MEF2 transcription factors are expressed in the myotome of developing somites and cooperatively activate skeletal muscle gene expression. The bHLH protein Twist is expressed throughout the epithelial somite and is subsequently excluded from the myotome. Ectopically expressed mouse Twist (Mtwist) was shown to inhibit myogenesis by blocking DNA binding by MyoD, by titrating E proteins, and by inhibiting trans-activation by MEF2. For inhibition of MEF2, Mtwist required heterodimerization with E proteins and an intact basic domain and carboxyl-terminus. Thus, Mtwist inhibits both families of myogenic regulators and may regulate myotome formation temporally or spatially.