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.

A cytosolic Ezh1 isoform modulates a PRC2-Ezh1 epigenetic adaptive response in postmitotic cells / B. Bodega, F. Marasca, V. Ranzani, A. Cherubini, F. Della Valle, M.V. Neguembor, M. Wassef, A. Zippo, C. Lanzuolo, M. Pagani, V. Orlando. - In: NATURE STRUCTURAL & MOLECULAR BIOLOGY. - ISSN 1545-9993. - 24:5(2017), pp. 444-452. [10.1038/nsmb.3392]

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

B. Bodega;F. Marasca;V. Ranzani;A. Cherubini;A. Zippo;M. Pagani;
2017

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.
English
Group protein EED; gene-expression; histone H3; muscle atrophy; actin polymerization; oxidative stress; stem-cells; polycomb; methylation; chromatin
Settore BIO/11 - Biologia Molecolare
Articolo
Esperti anonimi
Ricerca di base
Pubblicazione scientifica
2017
Nature Publishing Group
24
5
444
452
9
Pubblicato
Periodico con rilevanza internazionale
scopus
pubmed
crossref
Aderisco
info:eu-repo/semantics/article
A cytosolic Ezh1 isoform modulates a PRC2-Ezh1 epigenetic adaptive response in postmitotic cells / B. Bodega, F. Marasca, V. Ranzani, A. Cherubini, F. Della Valle, M.V. Neguembor, M. Wassef, A. Zippo, C. Lanzuolo, M. Pagani, V. Orlando. - In: NATURE STRUCTURAL & MOLECULAR BIOLOGY. - ISSN 1545-9993. - 24:5(2017), pp. 444-452. [10.1038/nsmb.3392]
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B. Bodega, F. Marasca, V. Ranzani, A. Cherubini, F. Della Valle, M.V. Neguembor, M. Wassef, A. Zippo, C. Lanzuolo, M. Pagani, V. Orlando
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/692961
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