A cytosolic Ezh1 isoform modulates a PRC2–Ezh1 epigenetic adaptive response in postmitotic cells

Beatrice Bodega, Federica Marasca, Valeria Ranzani, Alessandro Cherubini, Francesco Della Valle, Maria Victoria Neguembor, Michel Wassef, Alessio Zippo, Chiara Lanzuolo, Massimiliano Pagani, Valerio Orlando

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.
Original languageEnglish (US)
Pages (from-to)444-452
Number of pages9
JournalNature Structural & Molecular Biology
Volume24
Issue number5
DOIs
StatePublished - Mar 27 2017

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We 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.).

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