2026-06-03T08:12:50Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/149642025-06-17T10:45:34Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616
Repisalud
author
El Abdellaoui-Soussi, Fadoua
author
Yunes-Leites, Paula Sofia
author
Lopez-Maderuelo, Dolores
author
Garcia-Marques, Fernando
author
Vazquez, Jesus
author
Redondo, Juan Miguel
author
Gómez-Del Arco, Pablo
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia e Innovación (España)
funder
Comunidad de Madrid (España)
funder
Unión Europea. Fondo Social Europeo (ESF/FSE)
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
funder
Fundación ProCNIC
funder
Fundación La Caixa
2022-09-13T13:11:30Z
2022-09-13T13:11:30Z
2022-08-24
Int J Mol Sci. 2022 Aug 24;23(17):9565.
10.3390/ijms23179565
1422-0067
International journal of molecular sciences
36076959
http://hdl.handle.net/20.500.12105/14964
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.
eng
Chd4
NuRD
Znf219
Chromatin remodeling
Epigenetics
Heart
Arrhythmia
Interplay between the Chd4/NuRD Complex and the Transcription Factor Znf219 Controls Cardiac Cell Identity
research article
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Interplay Chd4_NuRDComplex_2022.pdf.txt