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...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2023-02-01
|
Series: | FEBS Open Bio |
Subjects: | |
Online Access: | https://doi.org/10.1002/2211-5463.13549 |
_version_ | 1811170862316912640 |
---|---|
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. |
first_indexed | 2024-04-10T17:04:54Z |
format | Article |
id | doaj.art-2fc31ce8ff1248488710dddf02bb9a8c |
institution | Directory Open Access Journal |
issn | 2211-5463 |
language | English |
last_indexed | 2024-04-10T17:04:54Z |
publishDate | 2023-02-01 |
publisher | Wiley |
record_format | Article |
series | FEBS Open Bio |
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 |
work_keys_str_mv | AT tsuyoshimorita actinrelatedprotein5suppressesthecooperativeactivationofcardiacgenetranscriptionbymyocardinandmef2 AT kenichirohayashi actinrelatedprotein5suppressesthecooperativeactivationofcardiacgenetranscriptionbymyocardinandmef2 |