title: An initial blueprint for myogenic differentiation.
abstract: We have combined genome-wide transcription factor binding and expression profiling to assemble a regulatory network controlling the myogenic differentiation program in mammalian cells. We identified a cadre of overlapping and distinct targets of the key myogenic regulatory factors (MRFs)--MyoD and myogenin--and Myocyte Enhancer Factor 2 (MEF2). We discovered that MRFs and MEF2 regulate a remarkably extensive array of transcription factor genes that propagate and amplify the signals initiated by MRFs. We found that MRFs play an unexpectedly wide-ranging role in directing the assembly and usage of the neuromuscular junction. Interestingly, these factors also prepare myoblasts to respond to diverse types of stress. Computational analyses identified novel combinations of factors that, depending on the differentiation state, might collaborate with MRFs. Our studies suggest unanticipated biological insights into muscle development and highlight new directions for further studies of genes involved in muscle repair and responses to stress and damage.
authors.affiliation: Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Blais
authors.forename: Mary
authors.initials: M
authors.lastname: Tsikitis
authors.forename: Diego
authors.initials: D
authors.lastname: Acosta-Alvear
authors.forename: Roded
authors.initials: R
authors.lastname: Sharan
authors.forename: Yuval
authors.initials: Y
authors.lastname: Kluger
authors.forename: Brian David
authors.initials: BD
authors.lastname: Dynlacht
mesh_terms: D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D004268:DNA-Binding Proteins; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics* / Q000502:physiology; D064326:MEF2 Transcription Factors; D024510:Muscle Development / Q000235:genetics* / Q000502:physiology; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D032446:Myoblasts / Q000502:physiology; D018006:Myogenic Regulatory Factors; D018008:Myogenin / Q000235:genetics* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D014157:Transcription Factors