The chromatin remodeling complex Chd4/NuRD controls striated muscle identity and metabolic homeostasis

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  • dc.contributor.author Gómez-Del Arco, Pablo
  • dc.contributor.author Perdiguero, Eusebio, 1968-
  • dc.contributor.author Muñoz Cánoves, Pura, 1962-
  • dc.contributor.author Redondo, Juan Miguel
  • dc.date.accessioned 2019-03-15T13:11:38Z
  • dc.date.available 2019-03-15T13:11:38Z
  • dc.date.issued 2016
  • dc.description.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.
  • dc.description.sponsorship We thank Drs. Richard Harvey (University of Sydney, Australia) and Michael Schneider (Imperial College, London, UK) for providing Nkx2.5cre/+ and α-MHCcre/+ transgenic lines, respectively, Dr. S. Bartlett for English editing, and Gemma Benito and Ana Guío for technical assistance. J.M.R. is supported by the Spanish Ministry of Economy and Competitiveness (Ministerio de Economía y Competitividad; SAF 2012 34296 and SAF 2015 63633-R), the Spanish Ministry of Health (Ministerio de Sanidad y Consumo) Red de Investigación Cardiovascular (RIC; grant RD06/0042/0022), and the Fundación La Marató TV3 (264/C/2012). The RIC also supports J.L.P. (RD12/0042/0005) and L.J.J.-B. (RD12/0042/0056). RIC grants are partially funded by FEDER funds. P.M.-C., J.A.E., and J.L.P. are supported by SAF2012-38547, SAF2015-67369-R, SAF2012-1207, and SAF2013-45543-R, respectively. E.P. and P.M.-C. were also supported by SAF2015-67369-R. NGS experiments were performed at the CNIC Genomics Unit. IF of adult hearts was performed at the Advanced Fluorescence Microscopy Unit of (IBMB-CSIC) Barcelona. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). R.A.-P. was supported by a Ramón y Cajal grant and is a holder of a Marie Curie grant (RA-P:UEO/MCA1108). M.Z. was a holder of a Marie Curie Outgoing International Fellowship (MOIF-CT-2006-039327), and P.G.A. was supported by a Ramón y Cajal grant from the Spanish Ministry of Education, Science and Sport.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Gómez-Del Arco P, Perdiguero E, Yunes-Leites PS, Acín-Pérez R, Zeini M, Garcia-Gomez A et al. The chromatin remodeling complex Chd4/NuRD controls striated muscle identity and metabolic homeostasis. Cell Metab. 2016;23(5):881-92. DOI 10.1016/j.cmet.2016.04.008
  • dc.identifier.doi http://dx.doi.org/10.1016/j.cmet.2016.04.008
  • dc.identifier.issn 1550-4131
  • dc.identifier.uri http://hdl.handle.net/10230/36846
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Cell Metabolism. 2016;23(5):881-92
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-34296
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-63633-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-38547
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SEV-2015-0505
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-67369-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-45543-R
  • dc.rights © Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.cmet.2016.04.008 that appeared in the journal Cell metabolism. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: https://www.elsevier.com/about/our-business/policies/open-access-licenses/elsevier-user-license
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://www.elsevier.com/open-access/userlicense/1.0/
  • dc.title The chromatin remodeling complex Chd4/NuRD controls striated muscle identity and metabolic homeostasis
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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