title: Distinct Activities of Myf5 and MyoD Indicate Separate Roles in Skeletal Muscle Lineage Specification and Differentiation.
abstract: Most transcription factor families contain highly related paralogs generated by gene duplication, and functional divergence is generally accomplished by activation of distinct sets of genes by each member. Here we compare the molecular functions of Myf5 and MyoD, two highly related bHLH transcription factors that regulate skeletal muscle specification and differentiation. We find that MyoD and Myf5 bind the same sites genome-wide but have distinct functions: Myf5 induces histone acetylation without Pol II recruitment or robust gene activation, whereas MyoD induces histone acetylation, recruits Pol II, and robustly activates gene transcription. Therefore, the initial specification of the muscle lineage by Myf5 occurs without significant induction of gene transcription. Transcription of the skeletal muscle program is then achieved by the subsequent expression of MyoD, which binds to the same sites as Myf5, indicating that each factor regulates distinct steps in gene initiation and transcription at a shared set of binding sites.
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: mconerly@fhcrc.org.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Conerly
authors.affiliation: Allen Brain Institute, Seattle, WA 98105, USA.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Jun Wen
authors.initials: JW
authors.lastname: Zhong
authors.affiliation: Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Groudine
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Neurology, University of Washington, School of Medicine, Seattle, WA 98105, USA. Electronic address: stapscot@fredhutch.org.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tapscott
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism*; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5