1. Developmental Biology
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Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice

  1. Shinichiro Hayashi
  2. Ichiro Manabe
  3. Yumi Suzuki
  4. Frédéric Relaix
  5. Yumiko Oishi  Is a corresponding author
  1. Tokyo Medical and Dental University, Japan
  2. Chiba University, Japan
  3. INSERM U955 IMRB-E10 UPEC, ENVA, EFS, 8 rue du general Sarrail, 94010 Creteil, France
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Cite this article as: eLife 2016;5:e17462 doi: 10.7554/eLife.17462

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 myogenin in vivo. Satellite cell-specific Klf5 deletion severely impaired muscle regeneration, and myotube formation was suppressed in Klf5-deleted cultured C2C12 myoblasts and satellite cells. Klf5 knockdown 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.

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Author details

  1. Shinichiro Hayashi

    Department of Cellular and Molecular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  2. Ichiro Manabe

    Department of Aging Research, Graduate School of Medicine, Chiba University, Chiba, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Yumi Suzuki

    Department of Cellular and Molecular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Frédéric Relaix

    INSERM U955 IMRB-E10 UPEC, ENVA, EFS, 8 rue du general Sarrail, 94010 Creteil, Creteil, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Yumiko Oishi

    Department of Cellular and Molecular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
    For correspondence
    yuooishi-circ@umin.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4761-0952

Funding

Japan Society for the Promotion of Science (26882020)

  • Shinichiro Hayashi

Japan Society for the Promotion of Science (25H10)

  • Yumiko Oishi

Nakatomi Foundation

  • Shinichiro Hayashi

Uehara Memorial Foundation

  • Shinichiro Hayashi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal experimentation was approved by the Experimental Animal Care and Use Committee of Tokyo Medical and Dental University (approval numbers 2013-027C12 and 0170280C).

Reviewing Editor

  1. Margaret Buckingham, Institut Pasteur, France

Publication history

  1. Received: May 6, 2016
  2. Accepted: October 13, 2016
  3. Accepted Manuscript published: October 15, 2016 (version 1)
  4. Version of Record published: October 21, 2016 (version 2)

Copyright

© 2016, Hayashi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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