title: MyoD Regulates Skeletal Muscle Oxidative Metabolism Cooperatively with Alternative NF-κB.
abstract: MyoD is a key regulator of skeletal myogenesis that directs contractile protein synthesis, but whether this transcription factor also regulates skeletal muscle metabolism has not been explored. In a genome-wide ChIP-seq analysis of skeletal muscle cells, we unexpectedly observed that MyoD directly binds to numerous metabolic genes, including those associated with mitochondrial biogenesis, fatty acid oxidation, and the electron transport chain. Results in cultured cells and adult skeletal muscle confirmed that MyoD regulates oxidative metabolism through multiple transcriptional targets, including PGC-1β, a master regulator of mitochondrial biogenesis. We find that PGC-1β expression is cooperatively regulated by MyoD and the alternative NF-κB signaling pathway. Bioinformatics evidence suggests that this cooperativity between MyoD and NF-κB extends to other metabolic genes as well. Together, these data identify MyoD as a regulator of the metabolic capacity of mature skeletal muscle to ensure that sufficient energy is available to support muscle contraction.
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University, Columbus, OH 43210, USA; Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shintaku
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Peterson
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Talbert
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University, Columbus, OH 43210, USA; Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jin-Mo
authors.initials: JM
authors.lastname: Gu
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Ladner
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Dustin R
authors.initials: DR
authors.lastname: Williams
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, Bethesda, MD 20892, USA.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Mousavi
authors.affiliation: Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
authors.forename: Ruoning
authors.initials: R
authors.lastname: Wang
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, Bethesda, MD 20892, USA.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sartorelli
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University, Columbus, OH 43210, USA. Electronic address: denis.guttridge@osumc.edu.
authors.forename: Denis C
authors.initials: DC
authors.lastname: Guttridge
mesh_terms: D000818:Animals; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009119:Muscle Contraction / Q000235:genetics; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism*; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D051841:Transcription Factor RelB / Q000235:genetics / Q000378:metabolism
chemical_list: D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D016328:NF-kappa B; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C497594:Relb protein, mouse; D051841:Transcription Factor RelB
keywords: MyoD; NF-kappaB; PGC-1beta; RelB; mitochondrial biogenesis; oxidative metabolism; ppargc1b; skeletal muscle