title: A cytosolic Ezh1 isoform modulates a PRC2-Ezh1 epigenetic adaptive response in postmitotic cells.
abstract: The 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.
authors.affiliation: Istituto Nazionale di Genetica Molecolare (INGM) Romeo and Enrica Invernizzi, Milan, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bodega
authors.affiliation: IRCSS Fondazione Santa Lucia, Epigenetics and Genome Reprogramming, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Marasca
authors.affiliation: Istituto Nazionale di Genetica Molecolare (INGM) Romeo and Enrica Invernizzi, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ranzani
authors.affiliation: Istituto Nazionale di Genetica Molecolare (INGM) Romeo and Enrica Invernizzi, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cherubini
authors.affiliation: Environmental Epigenetics Research Program, Division of Biological Environmental Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
authors.forename: Francesco
authors.initials: F
authors.lastname: Della Valle
authors.affiliation: Dulbecco Telethon Institute at San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Neguembor
authors.affiliation: Génétique et Biologie du Développement, Institut Curie, Inserm, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Wassef
authors.affiliation: Istituto Nazionale di Genetica Molecolare (INGM) Romeo and Enrica Invernizzi, Milan, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Zippo
authors.affiliation: CNR Institute of Cellular Biology and Neurobiology, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Lanzuolo
authors.affiliation: Istituto Nazionale di Genetica Molecolare (INGM) Romeo and Enrica Invernizzi, Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pagani
authors.affiliation: IRCSS Fondazione Santa Lucia, Epigenetics and Genome Reprogramming, Rome, Italy.|Environmental Epigenetics Research Program, Division of Biological Environmental Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
authors.forename: Valerio
authors.initials: V
authors.lastname: Orlando
mesh_terms: D002455:Cell Division; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; C103523:EZH1 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2