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dc.contributor.author | El Abdellaoui-Soussi, Fadoua | |
dc.contributor.author | Yunes-Leites, Paula Sofia | |
dc.contributor.author | Lopez-Maderuelo, Dolores | |
dc.contributor.author | Garcia-Marques, Fernando | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Redondo, Juan Miguel | |
dc.contributor.author | Gómez-Del Arco, Pablo | |
dc.date.accessioned | 2022-09-13T13:11:30Z | |
dc.date.available | 2022-09-13T13:11:30Z | |
dc.date.issued | 2022-08-24 | |
dc.identifier.citation | Int J Mol Sci. 2022 Aug 24;23(17):9565. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/14964 | |
dc.description.abstract | The sarcomere regulates striated muscle contraction. This structure is composed of several myofibril proteins, isoforms of which are encoded by genes specific to either the heart or skeletal muscle. The chromatin remodeler complex Chd4/NuRD regulates the transcriptional expression of these specific sarcomeric programs by repressing genes of the skeletal muscle sarcomere in the heart. Aberrant expression of skeletal muscle genes induced by the loss of Chd4 in the heart leads to sudden death due to defects in cardiomyocyte contraction that progress to arrhythmia and fibrosis. Identifying the transcription factors (TFs) that recruit Chd4/NuRD to repress skeletal muscle genes in the myocardium will provide important information for understanding numerous cardiac pathologies and, ultimately, pinpointing new therapeutic targets for arrhythmias and cardiomyopathies. Here, we sought to find Chd4 interactors and their function in cardiac homeostasis. We therefore describe a physical interaction between Chd4 and the TF Znf219 in cardiac tissue. Znf219 represses the skeletal-muscle sarcomeric program in cardiomyocytes in vitro and in vivo, similarly to Chd4. Aberrant expression of skeletal-muscle sarcomere proteins in mouse hearts with knocked down Znf219 translates into arrhythmias, accompanied by an increase in PR interval. These data strongly suggest that the physical and genetic interaction of Znf219 and Chd4 in the mammalian heart regulates cardiomyocyte identity and myocardial contraction. | es_ES |
dc.description.sponsorship | J.V. was supported by the Spanish Ministry of Science and Innovation (PGC2018-097019-B-I00 and PID2021-122348NB-I00), UE Funds and Micinn-Inst Carlos III (PMP21_00057) and “la Caixa” Banking Foundation (project codes HR17-00247 and HR22-00253). J.M.R. was supported by the La Caixa Banking Foundation (project code HR18-00068), the Spanish Ministry of Science and Innovation grant RTI2018-099246-B-I00 (MICIU/AEI/FEDER, UE); the Comunidad de Madrid and European Social Fund (ESF) grant AORTASANA-CM (B2017/BMD-3676); and the Instituto de Salud Carlos III (ISCIII) (CIBER-CVCB16/11/00264). PG-A was supported by Spanish Ministry of Science and Innovation (grants SAF2016-77816-P and PID2020-114773GB-I00). The CNIC is supported by Instituto de Salud Carlos III (ISCIII), the Spanish Ministry of Science and Innovation and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by Spanish Ministry of Science and Innovation AEI/10.13039/501100011033). FAS is supported by a Science and Innovation Fellowship (BES-2017-080629). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Chd4 | es_ES |
dc.subject | NuRD | es_ES |
dc.subject | Znf219 | es_ES |
dc.subject | Chromatin remodeling | es_ES |
dc.subject | Epigenetics | es_ES |
dc.subject | Heart | es_ES |
dc.subject | Arrhythmia | es_ES |
dc.subject.mesh | Mi-2 Nucleosome Remodeling and Deacetylase Complex | es_ES |
dc.subject.mesh | Transcription Factors | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Gene Expression Regulation | es_ES |
dc.subject.mesh | Mammals | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Muscle Proteins | es_ES |
dc.subject.mesh | Myocytes, Cardiac | es_ES |
dc.subject.mesh | Nucleosomes | es_ES |
dc.title | Interplay between the Chd4/NuRD Complex and the Transcription Factor Znf219 Controls Cardiac Cell Identity | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution 4.0 International | * |
dc.identifier.pubmedID | 36076959 | es_ES |
dc.format.volume | 23 | es_ES |
dc.format.number | 17 | es_ES |
dc.format.page | 9565 | es_ES |
dc.identifier.doi | 10.3390/ijms23179565 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Social Europeo (ESF/FSE) | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España) | es_ES |
dc.contributor.funder | Fundación ProCNIC | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1422-0067 | es_ES |
dc.relation.publisherversion | https://doi.org/10.3390/ijms23179565 | es_ES |
dc.identifier.journal | International journal of molecular sciences | es_ES |
dc.repisalud.centro | ISCIII::Instituto de Investigación de Enfermedades Raras | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/CE/B2017/BMD-3676 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PGC2018-097019-B-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2021-122348NB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PMP21%2F00057/ES/DIANAS TERAPEUTICAS Y BIOMARCADORES PARA LA MEDICINA DE PRECISION EN MAFLD (PREMED-MAFLD)/ | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RTI2018-099246-B-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SAF2016-77816-P | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2020-114773GB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/CEX2020-001041-S | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/AEI/10.13039/501100011033 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/CIBER-CVCB16/11/00264 | es_ES |