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http://hdl.handle.net/2445/127975
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DC Field | Value | Language |
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dc.contributor.author | Marjanović, Melanija Posavec | - |
dc.contributor.author | Hurtado-Bagès, Sarah, 1990- | - |
dc.contributor.author | Lassi, Maximilian | - |
dc.contributor.author | Varela Vázquez, Vanesa | - |
dc.contributor.author | Malinverni, Roberto | - |
dc.contributor.author | Delage, Hélène | - |
dc.contributor.author | Navarro, Miriam | - |
dc.contributor.author | Corujo García, David | - |
dc.contributor.author | Guberovic, Iva | - |
dc.contributor.author | Douet, Julien | - |
dc.contributor.author | Gama-Perez, Pau | - |
dc.contributor.author | García-Roves, Pablo M. (Pablo Miguel) | - |
dc.contributor.author | Ahel, Ivan | - |
dc.contributor.author | Ladurner, Andreas G. | - |
dc.contributor.author | Yanes, Oscar | - |
dc.contributor.author | Bouvet, Philippe | - |
dc.contributor.author | Suelves Esteban, Mònica | - |
dc.contributor.author | Teperino, Raffaele | - |
dc.contributor.author | Pospisilik, J. Andrew | - |
dc.contributor.author | Buschbeck, Marcus | - |
dc.date.accessioned | 2019-02-06T15:25:05Z | - |
dc.date.available | 2019-02-06T15:25:05Z | - |
dc.date.issued | 2017-10-09 | - |
dc.identifier.issn | 1545-9993 | - |
dc.identifier.uri | http://hdl.handle.net/2445/127975 | - |
dc.description.abstract | Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A.1.1 contains a macrodomain able to bind NAD+ derived metabolites. Here, we report that macroH2A.1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing. Importantly, myotubes lacking macroH2A.1.1 display a defect in mitochondrial respiratory capacity. We find that the metabolite-interacting macrodomain is essential for sustaining optimal mitochondrial function, but dispensable for gene regulation. Through direct binding, macroH2A.1.1 inhibits basal poly-ADP ribose polymerase 1 activity and thus reduces nuclear NAD+ consumption. Consequentially, accumulation of the NAD+ precursor NMN allows the maintenance of mitochondrial NAD+ pools critical for respiration. Our data indicate that macroH2A.1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD+ consumption and establishing a buffer of NAD+ precursors in differentiated cells. | - |
dc.format.extent | 9 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1038/nsmb.3481 | - |
dc.relation.ispartof | Nature Structural & Molecular Biology, 2017, vol. 24, num. 11, p. 902-910 | - |
dc.relation.uri | https://doi.org/10.1038/nsmb.3481 | - |
dc.rights | (c) Marjanovic, Melanija Posavec et al., 2017 | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Nuclis cel·lulars | - |
dc.subject.classification | Metabolisme | - |
dc.subject.classification | Expressió gènica | - |
dc.subject.classification | Histones | - |
dc.subject.classification | Mitocondris | - |
dc.subject.other | Cell nuclei | - |
dc.subject.other | Metabolism | - |
dc.subject.other | Gene expression | - |
dc.subject.other | Histones | - |
dc.subject.other | Mitochondria | - |
dc.title | MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 673801 | - |
dc.date.updated | 2019-02-06T15:25:05Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/682679/EU//DismantlingNoise | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/675610/EU//ChroMe | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/281641/EU//METABOLICPOLYCOMBICS | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 28991266 | - |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Publicacions de projectes de recerca finançats per la UE |
Files in This Item:
File | Description | Size | Format | |
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673801.pdf | 1.95 MB | Adobe PDF | View/Open |
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