Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice

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 af...

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Main Authors: Shinichiro Hayashi, Ichiro Manabe, Yumi Suzuki, Frédéric Relaix, Yumiko Oishi
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2016-10-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/17462
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author Shinichiro Hayashi
Ichiro Manabe
Yumi Suzuki
Frédéric Relaix
Yumiko Oishi
author_facet Shinichiro Hayashi
Ichiro Manabe
Yumi Suzuki
Frédéric Relaix
Yumiko Oishi
author_sort Shinichiro Hayashi
collection DOAJ
description 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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spelling doaj.art-c6706733954b4408b641d195094071e82022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2016-10-01510.7554/eLife.17462Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in miceShinichiro Hayashi0Ichiro Manabe1Yumi Suzuki2Frédéric Relaix3Yumiko Oishi4https://orcid.org/0000-0002-4761-0952Department of Cellular and Molecular Medicine, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Aging Research, Graduate School of Medicine, Chiba University, Chiba, JapanDepartment of Cellular and Molecular Medicine, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, JapanINSERM U955 IMRB-E10 UPEC, ENVA, EFS, Creteil, FranceDepartment of Cellular and Molecular Medicine, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, JapanKrüppel-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.https://elifesciences.org/articles/17462satellite cellmuscle differentiationmuscle regenerationKrüppel-like factor
spellingShingle Shinichiro Hayashi
Ichiro Manabe
Yumi Suzuki
Frédéric Relaix
Yumiko Oishi
Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice
eLife
satellite cell
muscle differentiation
muscle regeneration
Krüppel-like factor
title Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice
title_full Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice
title_fullStr Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice
title_full_unstemmed Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice
title_short Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice
title_sort klf5 regulates muscle differentiation by directly targeting muscle specific genes in cooperation with myod in mice
topic satellite cell
muscle differentiation
muscle regeneration
Krüppel-like factor
url https://elifesciences.org/articles/17462
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AT ichiromanabe klf5regulatesmuscledifferentiationbydirectlytargetingmusclespecificgenesincooperationwithmyodinmice
AT yumisuzuki klf5regulatesmuscledifferentiationbydirectlytargetingmusclespecificgenesincooperationwithmyodinmice
AT fredericrelaix klf5regulatesmuscledifferentiationbydirectlytargetingmusclespecificgenesincooperationwithmyodinmice
AT yumikooishi klf5regulatesmuscledifferentiationbydirectlytargetingmusclespecificgenesincooperationwithmyodinmice