MyoR: a muscle-restricted basic helix-loop-helix transcription factor that antagonizes the actions of MyoD.
Skeletal muscle development is controlled by a family of muscle-specific basic helix-loop-helix (bHLH) transcription factors that activate muscle genes by binding E-boxes (CANNTG) as heterodimers with ubiquitous bHLH proteins, called E proteins. Myogenic bHLH factors are expressed in proliferating undifferentiated myoblasts, but they do not initiate myogenesis until myoblasts exit the cell cycle. We describe a bHLH protein, MyoR (for myogenic repressor), that is expressed in undifferentiated myoblasts in culture and is down-regulated during differentiation. MyoR is also expressed specifically in the skeletal muscle lineage between days 10.5 and 16.5 of mouse embryogenesis and down-regulated thereafter during the period of secondary myogenesis. MyoR forms heterodimers with E proteins that bind the same DNA sequence as myogenic bHLH/E protein heterodimers, but MyoR acts as a potent transcriptional repressor that blocks myogenesis and activation of E-box-dependent muscle genes. These results suggest a role for MyoR as a lineage-restricted transcriptional repressor of the muscle differentiation program.
Lu
J
J
Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75235-9148, USA.
Webb
R
R
Richardson
J A
JA
Olson
E N
EN
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics; D019281:Dimerization; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D024510:Muscle Development; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000254:growth & development*; D017570:MyoD Protein / Q000037:antagonists & inhibitors*; D018008:Myogenin / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D014162:Transfection / Q000235:genetics
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D017570:MyoD Protein; C503801:Myog protein, mouse; D018008:Myogenin; C498449:Ostn protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors