title: Myogenin resides in the nucleus and acquires high affinity for a conserved enhancer element on heterodimerization.
abstract: Myogenin is a member of a family of muscle-specific factors that can activate the muscle differentiation program in nonmyogenin cells. Using antibodies directed against unique domains of myogenin, we show in the present study that myogenin resides in the nucleus of differentiated muscle cells. Myogenin translated in vitro does not exhibit detectable DNA binding activity; however, when dimerized with the ubiquitous enhancer-binding factor E12, it acquires high affinity for an element in the core of the muscle creatine kinase (MCK) enhancer that is conserved among many muscle-specific genes. Antibody disruption experiments show that myogenin, synthesized during differentiation of the BC3H1 and C2 muscle cell lines, is part of a complex that binds to the same site in the MCK enhancer as myogenin-E12 translated in vitro. Mutagenesis of the myogenin-E12-binding site in the MCK enhancer abolishes binding of the heterodimer and prevents trans-activation of the enhancer by myogenin. The properties of myogenin suggest that its functions as a sequence-specific DNA-binding factor that interacts directly with muscle-specific genes during myogenesis. The dependence of myogenin on E12 for high-affinity DNA binding activity also suggests that the susceptibility of various cell types to the actions of myogenin may be influenced by the cellular factors with which it may interact.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas, MD Anderson Cancer Center, Houston 77030.
authors.forename: T J
authors.initials: TJ
authors.lastname: Brennan
authors.forename: E N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003402:Creatine Kinase / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005455:Fluorescent Antibody Technique; D008745:Methylation; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009132:Muscles / Q000166:cytology* / Q000378:metabolism; D009154:Mutation; D018008:Myogenin; D011233:Precipitin Tests; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D018008:Myogenin; D014157:Transcription Factors; D004247:DNA; D003402:Creatine Kinase