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The Chromatin Remodeling Complex Chd4/NuRD Controls Striated Muscle Identity and Metabolic Homeostasis

Cell Metabolism, ISSN: 1550-4131, Vol: 23, Issue: 5, Page: 881-892
2016
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Descrito el mecanismo que hace latir al corazón

Científicos de la UAM y el CNIC han descubierto que la proteína Chd4 desempeña un papel fundamental en el mantenimiento de la homeostasis y la identidad de los tejidos musculares estriados del corazón y el músculo esquelético. Las conclusiones de este trabajo, realizado en colaboración con otros centros, se han publicado en la revista Cell Metabolism.

Article Description

Heart muscle maintains blood circulation, while skeletal muscle powers skeletal movement. Despite having similar myofibrilar sarcomeric structures, these striated muscles differentially express specific sarcomere components to meet their distinct contractile requirements. The mechanism responsible is still unclear. We show here that preservation of the identity of the two striated muscle types depends on epigenetic repression of the alternate lineage gene program by the chromatin remodeling complex Chd4/NuRD. Loss of Chd4 in the heart triggers aberrant expression of the skeletal muscle program, causing severe cardiomyopathy and sudden death. Conversely, genetic depletion of Chd4 in skeletal muscle causes inappropriate expression of cardiac genes and myopathy. In both striated tissues, mitochondrial function was also dependent on the Chd4/NuRD complex. We conclude that an epigenetic mechanism controls cardiac and skeletal muscle structural and metabolic identities and that loss of this regulation leads to hybrid striated muscle tissues incompatible with life.

Bibliographic Details

Gómez-Del Arco, Pablo; Perdiguero, Eusebio; Yunes-Leites, Paula Sofia; Acín-Pérez, Rebeca; Zeini, Miriam; Garcia-Gomez, Antonio; Sreenivasan, Krishnamoorthy; Jiménez-Alcázar, Miguel; Segalés, Jessica; López-Maderuelo, Dolores; Ornés, Beatriz; Jiménez-Borreguero, Luis Jesús; D'Amato, Gaetano; Enshell-Seijffers, David; Morgan, Bruce; Georgopoulos, Katia; Islam, Abul B M M K; Braun, Thomas; de la Pompa, José Luis; Kim, Johnny; Enriquez, José A; Ballestar, Esteban; Muñoz-Cánoves, Pura; Redondo, Juan Miguel

Elsevier BV

Biochemistry, Genetics and Molecular Biology

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