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

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

doi:10.1016/j.cmet.2016.04.008

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

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

Bar-Ilan University - Azrieli Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	881-892
Number of pages	12
Journal	Cell Metabolism
Volume	23
Issue number	5
DOIs	https://doi.org/10.1016/j.cmet.2016.04.008
State	Published - 10 May 2016

All Science Journal Classification (ASJC) codes

Physiology
Molecular Biology
Cell Biology

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Gómez-Del Arco, P., Perdiguero, E., Yunes-Leites, P. S., Acín-Pérez, R., Zeini, M., Garcia-Gomez, A., Sreenivasan, K., Jiménez-Alcázar, M., Segalés, J., López-Maderuelo, D., Ornés, B., Jiménez-Borreguero, L. J., D'Amato, G., Enshell-Seijffers, D., Morgan, B., Georgopoulos, K., Islam, A. B. M. M. K., Braun, T., De La Pompa, J. L., ... Redondo, J. M. (2016). The Chromatin Remodeling Complex Chd4/NuRD Controls Striated Muscle Identity and Metabolic Homeostasis. Cell Metabolism, 23(5), 881-892. https://doi.org/10.1016/j.cmet.2016.04.008

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title = "The Chromatin Remodeling Complex Chd4/NuRD Controls Striated Muscle Identity and Metabolic Homeostasis",

abstract = "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.",

author = "{G{\'o}mez-Del Arco}, Pablo and Eusebio Perdiguero and Yunes-Leites, {Paula Sofia} and Rebeca Ac{\'i}n-P{\'e}rez and Miriam Zeini and Antonio Garcia-Gomez and Krishnamoorthy Sreenivasan and Miguel Jim{\'e}nez-Alc{\'a}zar and Jessica Segal{\'e}s and Dolores L{\'o}pez-Maderuelo and Beatriz Orn{\'e}s and Jim{\'e}nez-Borreguero, {Luis Jes{\'u}s} and Gaetano D'Amato and David Enshell-Seijffers and Bruce Morgan and Katia Georgopoulos and Islam, {Abul B.M.M.K.} and Thomas Braun and {De La Pompa}, {Jos{\'e} Luis} and Johnny Kim and Enriquez, {Jos{\'e} A.} and Esteban Ballestar and Pura Mu{\~n}oz-C{\'a}noves and Redondo, {Juan Miguel}",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = may,

day = "10",

doi = "10.1016/j.cmet.2016.04.008",

language = "الإنجليزيّة",

volume = "23",

pages = "881--892",

journal = "Cell Metabolism",

issn = "1550-4131",

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Gómez-Del Arco, P, Perdiguero, E, Yunes-Leites, PS, Acín-Pérez, R, Zeini, M, Garcia-Gomez, A, Sreenivasan, K, Jiménez-Alcázar, M, Segalés, J, López-Maderuelo, D, Ornés, B, Jiménez-Borreguero, LJ, D'Amato, G, Enshell-Seijffers, D, Morgan, B, Georgopoulos, K, Islam, ABMMK, Braun, T, De La Pompa, JL, Kim, J, Enriquez, JA, Ballestar, E, Muñoz-Cánoves, P & Redondo, JM 2016, 'The Chromatin Remodeling Complex Chd4/NuRD Controls Striated Muscle Identity and Metabolic Homeostasis', Cell Metabolism, vol. 23, no. 5, pp. 881-892. https://doi.org/10.1016/j.cmet.2016.04.008

TY - JOUR

T1 - The Chromatin Remodeling Complex Chd4/NuRD Controls Striated Muscle Identity and Metabolic Homeostasis

AU - Gómez-Del Arco, Pablo

AU - Perdiguero, Eusebio

AU - Yunes-Leites, Paula Sofia

AU - Acín-Pérez, Rebeca

AU - Zeini, Miriam

AU - Garcia-Gomez, Antonio

AU - Sreenivasan, Krishnamoorthy

AU - Jiménez-Alcázar, Miguel

AU - Segalés, Jessica

AU - López-Maderuelo, Dolores

AU - Ornés, Beatriz

AU - Jiménez-Borreguero, Luis Jesús

AU - D'Amato, Gaetano

AU - Enshell-Seijffers, David

AU - Morgan, Bruce

AU - Georgopoulos, Katia

AU - Islam, Abul B.M.M.K.

AU - Braun, Thomas

AU - De La Pompa, José Luis

AU - Kim, Johnny

AU - Enriquez, José A.

AU - Ballestar, Esteban

AU - Muñoz-Cánoves, Pura

AU - Redondo, Juan Miguel

PY - 2016/5/10

Y1 - 2016/5/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84966601466&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2016.04.008

DO - 10.1016/j.cmet.2016.04.008

M3 - مقالة

C2 - 27166947

SN - 1550-4131

VL - 23

SP - 881

EP - 892

JO - Cell Metabolism

JF - Cell Metabolism

IS - 5

ER -

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

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