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dc.contributor.authorBodega, Beatrice
dc.contributor.authorMarasca, Federica
dc.contributor.authorRanzani, Valeria
dc.contributor.authorCherubini, Alessandro
dc.contributor.authorValle, Francesco Della
dc.contributor.authorNeguembor, Maria Victoria
dc.contributor.authorWassef, Michel
dc.contributor.authorZippo, Alessio
dc.contributor.authorLanzuolo, Chiara
dc.contributor.authorPagani, Massimiliano
dc.contributor.authorOrlando, Valerio
dc.date.accessioned2017-05-31T11:23:04Z
dc.date.available2017-05-31T11:23:04Z
dc.date.issued2017-03-27
dc.identifier.citationBodega B, Marasca F, Ranzani V, Cherubini A, Della Valle F, et al. (2017) A cytosolic Ezh1 isoform modulates a PRC2–Ezh1 epigenetic adaptive response in postmitotic cells. Nature Structural & Molecular Biology 24: 444–452. Available: http://dx.doi.org/10.1038/nsmb.3392.
dc.identifier.issn1545-9993
dc.identifier.issn1545-9985
dc.identifier.doi10.1038/nsmb.3392
dc.identifier.urihttp://hdl.handle.net/10754/623777
dc.description.abstractThe evolution of chromatin-based epigenetic cell memory may be driven not only by the necessity for cells to stably maintain transcription programs, but also by the need to recognize signals and allow plastic responses to environmental stimuli. The mechanistic role of the epigenome in adult postmitotic tissues, however, remains largely unknown. In vertebrates, two variants of the Polycomb repressive complex (PRC2-Ezh2 and PRC2-Ezh1) control gene silencing via methylation of histone H3 on Lys27 (H3K27me). Here we describe a reversible mechanism that involves a novel isoform of Ezh1 (Ezh1β). Ezh1β lacks the catalytic SET domain and acts in the cytoplasm of skeletal muscle cells to control nuclear PRC2-Ezh1 activity in response to atrophic oxidative stress, by regulating Eed assembly with Suz12 and Ezh1α (the canonical isoform) at their target genes. We report a novel PRC2-Ezh1 function that utilizes Ezh1β as an adaptive stress sensor in the cytoplasm, thus allowing postmitotic cells to maintain tissue integrity in response to environmental changes.
dc.description.sponsorshipWe are grateful to C. Desplan, P. Sassone-Corsi, D. Gabellini, E. Battaglioli and S. Biffo for discussions and critical revision of the manuscript; G. Natoli (IFOM-IEO Campus, Milan, Italy) for sharing the Jmjd3 antibody; M. Mora (“Cells, tissues and DNA from patients with neuromuscular diseases” Telethon Biobank, Milan, Italy) for providing human primary myoblasts; R. Margueron (Institute Curie, Paris, France) for providing pCDNA-4TO-Ezh1α-HA plasmid; Sequentia Biotech SL, R. Bonnal and C. Cheroni for bioinformatical support; and M. Moro and M.C. Crosti for technical assistance with cell sorting. This work was supported by the EPIGEN Italian flagship program and King Abdullah University of Science and Technology (KAUST) (to V.O.).
dc.publisherSpringer Nature
dc.relation.urlhttp://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.3392.html
dc.titleA cytosolic Ezh1 isoform modulates a PRC2–Ezh1 epigenetic adaptive response in postmitotic cells
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.identifier.journalNature Structural & Molecular Biology
dc.contributor.institutionIstituto Nazionale di Genetica Molecolare (INGM) Romeo and Enrica Invernizzi, Milan, Italy.
dc.contributor.institutionIRCSS Fondazione Santa Lucia, Epigenetics and Genome Reprogramming, Rome, Italy.
dc.contributor.institutionDulbecco Telethon Institute at San Raffaele Scientific Institute, Milan, Italy.
dc.contributor.institutionGénétique et Biologie du Développement, Institut Curie, Inserm, Paris, France.
dc.contributor.institutionCNR Institute of Cellular Biology and Neurobiology, Rome, Italy.
kaust.personValle, Francesco Della
kaust.personOrlando, Valerio
dc.date.published-online2017-03-27
dc.date.published-print2017-05


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