Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice
- Tokyo Medical and Dental University, Japan
- Chiba University, Japan
- INSERM U955 IMRB-E10 UPEC, ENVA, EFS, 8 rue du general Sarrail, 94010 Creteil, France
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.
Data availability
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Klf5 regulates muscle differentiation via directly targeted muscle-specific genes in cooperation with MyoDPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE80812).
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Genome-wide analysis of gene expression during differentiation in C2C12 cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE20059).
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Alternate exon switching establishes a tissue-specific transcription factor to mediate temporal activation of gene expression during differentiationPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE43223).
Article and author information
Author details
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).
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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Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice
eLife 5:e17462.
https://doi.org/10.7554/eLife.17462
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