Actin‐related protein 5 suppresses the cooperative activation of cardiac gene transcription by myocardin and MEF2

MYOCD is a transcription factor important for cardiac and smooth muscle development. We previously identified that actin‐related protein 5 (ARP5) binds to the N‐terminus of MYOCD. Here, we demonstrate that ARP5 inhibits the cooperative action of the cardiac‐specific isoform of MYOCD with MEF2. ARP5...

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Main Authors: Tsuyoshi Morita, Ken'ichiro Hayashi
Format: Article
Language:English
Published: Wiley 2023-02-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.13549
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author Tsuyoshi Morita
Ken'ichiro Hayashi
author_facet Tsuyoshi Morita
Ken'ichiro Hayashi
author_sort Tsuyoshi Morita
collection DOAJ
description MYOCD is a transcription factor important for cardiac and smooth muscle development. We previously identified that actin‐related protein 5 (ARP5) binds to the N‐terminus of MYOCD. Here, we demonstrate that ARP5 inhibits the cooperative action of the cardiac‐specific isoform of MYOCD with MEF2. ARP5 overexpression in murine hearts induced cardiac hypertrophy and fibrosis, whereas ARP5 knockdown in P19CL6 cells significantly increased cardiac gene expression. ARP5 was found to bind to a MEF2‐binding motif of cardiac MYOCD and inhibit MEF2‐mediated transactivation by MYOCD. RNA‐seq analysis revealed 849 genes that are upregulated by MYOCD‐MEF2 and 650 genes that are repressed by ARP5. ARP5 expression increased with cardiomyopathy and was negatively correlated with the expression of Tnnt2 and Ttn, which were regulated by cardiac MYOCD‐MEF2. Overall, our data suggest that ARP5 is a potential suppressor of cardiac MYOCD during physiological and pathological processes.
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spelling doaj.art-2fc31ce8ff1248488710dddf02bb9a8c2023-02-06T06:18:51ZengWileyFEBS Open Bio2211-54632023-02-0113236337910.1002/2211-5463.13549Actin‐related protein 5 suppresses the cooperative activation of cardiac gene transcription by myocardin and MEF2Tsuyoshi Morita0Ken'ichiro Hayashi1Department of Biology Wakayama Medical University JapanDepartment of Ophthalmology Yamaguchi University Graduate School of Medicine JapanMYOCD is a transcription factor important for cardiac and smooth muscle development. We previously identified that actin‐related protein 5 (ARP5) binds to the N‐terminus of MYOCD. Here, we demonstrate that ARP5 inhibits the cooperative action of the cardiac‐specific isoform of MYOCD with MEF2. ARP5 overexpression in murine hearts induced cardiac hypertrophy and fibrosis, whereas ARP5 knockdown in P19CL6 cells significantly increased cardiac gene expression. ARP5 was found to bind to a MEF2‐binding motif of cardiac MYOCD and inhibit MEF2‐mediated transactivation by MYOCD. RNA‐seq analysis revealed 849 genes that are upregulated by MYOCD‐MEF2 and 650 genes that are repressed by ARP5. ARP5 expression increased with cardiomyopathy and was negatively correlated with the expression of Tnnt2 and Ttn, which were regulated by cardiac MYOCD‐MEF2. Overall, our data suggest that ARP5 is a potential suppressor of cardiac MYOCD during physiological and pathological processes.https://doi.org/10.1002/2211-5463.13549actin‐related proteinARP5cardiomyopathyMEF2myocardinMYOCD
spellingShingle Tsuyoshi Morita
Ken'ichiro Hayashi
Actin‐related protein 5 suppresses the cooperative activation of cardiac gene transcription by myocardin and MEF2
FEBS Open Bio
actin‐related protein
ARP5
cardiomyopathy
MEF2
myocardin
MYOCD
title Actin‐related protein 5 suppresses the cooperative activation of cardiac gene transcription by myocardin and MEF2
title_full Actin‐related protein 5 suppresses the cooperative activation of cardiac gene transcription by myocardin and MEF2
title_fullStr Actin‐related protein 5 suppresses the cooperative activation of cardiac gene transcription by myocardin and MEF2
title_full_unstemmed Actin‐related protein 5 suppresses the cooperative activation of cardiac gene transcription by myocardin and MEF2
title_short Actin‐related protein 5 suppresses the cooperative activation of cardiac gene transcription by myocardin and MEF2
title_sort actin related protein 5 suppresses the cooperative activation of cardiac gene transcription by myocardin and mef2
topic actin‐related protein
ARP5
cardiomyopathy
MEF2
myocardin
MYOCD
url https://doi.org/10.1002/2211-5463.13549
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AT kenichirohayashi actinrelatedprotein5suppressesthecooperativeactivationofcardiacgenetranscriptionbymyocardinandmef2