title: Transcriptional dominance of Pax7 in adult myogenesis is due to high-affinity recognition of homeodomain motifs.
abstract: Pax3 and Pax7 regulate stem cell function in skeletal myogenesis. However, molecular insight into their distinct roles has remained elusive. Using gene expression data combined with genome-wide binding-site analysis, we show that both Pax3 and Pax7 bind identical DNA motifs and jointly activate a large panel of genes involved in muscle stem cell function. Surprisingly, in adult myoblasts Pax3 binds a subset (6.4%) of Pax7 targets. Despite a significant overlap in their transcriptional network, Pax7 regulates distinct panels of genes involved in the promotion of proliferation and inhibition of myogenic differentiation. We show that Pax7 has a higher binding affinity to the homeodomain-binding motif relative to Pax3, suggesting that intrinsic differences in DNA binding contribute to the observed functional difference between Pax3 and Pax7 binding in myogenesis. Together, our data demonstrate distinct attributes of Pax7 function and provide mechanistic insight into the nonredundancy of Pax3 and Pax7 in muscle development.
authors.affiliation: Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, and Department of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
authors.forename: Vahab D
authors.initials: VD
authors.lastname: Soleimani
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Punch
authors.forename: Yoh-ichi
authors.initials: Y
authors.lastname: Kawabe
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Jones
authors.forename: Gareth A
authors.initials: GA
authors.lastname: Palidwor
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Porter
authors.forename: Joe W
authors.initials: JW
authors.lastname: Cross
authors.forename: Jaime J
authors.initials: JJ
authors.lastname: Carvajal
authors.forename: Christel E M
authors.initials: CE
authors.lastname: Kockx
authors.forename: Wilfred F J
authors.initials: WF
authors.lastname: van IJcken
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Perkins
authors.forename: Peter W J
authors.initials: PW
authors.lastname: Rigby
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rudnicki
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor / Q000378:metabolism*; D051761:Paired Box Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D018398:Homeodomain Proteins; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; C497322:Pax7 protein, mouse; C068686:Pax3 protein, mouse