title: Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice.
abstract: Krüppel-like factor 5 (Klf5) is a zinc-finger transcription factor that controls various biological processes, including cell proliferation and differentiation. We show that Klf5 is also an essential mediator of skeletal muscle regeneration and myogenic differentiation. During muscle regeneration after injury (cardiotoxin injection), Klf5 was induced in the nuclei of differentiating myoblasts and newly formed myofibers expressing myogeninin vivo. Satellite cell-specificKlf5deletion severely impaired muscle regeneration, and myotube formation was suppressed inKlf5-deleted cultured C2C12 myoblasts and satellite cells.Klf5knockdown suppressed induction of muscle differentiation-related genes, including myogenin. Klf5 ChIP-seq revealed that Klf5 binding overlaps that of MyoD and Mef2, and Klf5 physically associates with both MyoD and Mef2. In addition, MyoD recruitment was greatly reduced in the absence of Klf5. These results indicate that Klf5 is an essential regulator of skeletal muscle differentiation, acting in concert with myogenic transcription factors such as MyoD and Mef2.
authors.affiliation: Department of Cellular and Molecular Medicine, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Aging Research, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Manabe
authors.affiliation: Department of Cellular and Molecular Medicine, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: INSERM U955 IMRB-E10 UPEC, ENVA, EFS, Creteil, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Relaix
authors.affiliation: Department of Cellular and Molecular Medicine, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yumiko
authors.identifier: 0000-0002-4761-0952
authors.initials: Y
authors.lastname: Oishi
mesh_terms: D000818:Animals; D054715:Cardiotoxins / Q000008:administration & dosage; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D064326:MEF2 Transcription Factors / Q000235:genetics; D051379:Mice; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D012038:Regeneration / Q000235:genetics; D032496:Satellite Cells, Skeletal Muscle
chemical_list: D054715:Cardiotoxins; C118391:Klf5 protein, mouse; D051741:Kruppel-Like Transcription Factors; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein
keywords: Krüppel-like factor; developmental biology; mouse; muscle differentiation; muscle regeneration; satellite cell; stem cells