An initial blueprint for myogenic differentiation.
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.
Blais
Alexandre
A
Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, New York 10016, USA.
Tsikitis
Mary
M
Acosta-Alvear
Diego
D
Sharan
Roded
R
Kluger
Yuval
Y
Dynlacht
Brian David
BD
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
D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D014157:Transcription Factors