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Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair

H3K9 methylation maintains cell identity orchestrating stable silencing and anchoring of alternate fate genes within the heterochromatic compartment underneath the nuclear lamina (NL). However, how cell type–specific genomic regions are specifically targeted to the NL is still elusive. Using fibro-a...

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Autores principales: Biferali, Beatrice, Bianconi, Valeria, Perez, Daniel Fernandez, Kronawitter, Sophie Pöhle, Marullo, Fabrizia, Maggio, Roberta, Santini, Tiziana, Polverino, Federica, Biagioni, Stefano, Summa, Vincenzo, Toniatti, Carlo, Pasini, Diego, Stricker, Sigmar, Di Fabio, Romano, Chiacchiera, Fulvio, Peruzzi, Giovanna, Mozzetta, Chiara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172132/
https://www.ncbi.nlm.nih.gov/pubmed/34078594
http://dx.doi.org/10.1126/sciadv.abd9371
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author Biferali, Beatrice
Bianconi, Valeria
Perez, Daniel Fernandez
Kronawitter, Sophie Pöhle
Marullo, Fabrizia
Maggio, Roberta
Santini, Tiziana
Polverino, Federica
Biagioni, Stefano
Summa, Vincenzo
Toniatti, Carlo
Pasini, Diego
Stricker, Sigmar
Di Fabio, Romano
Chiacchiera, Fulvio
Peruzzi, Giovanna
Mozzetta, Chiara
author_facet Biferali, Beatrice
Bianconi, Valeria
Perez, Daniel Fernandez
Kronawitter, Sophie Pöhle
Marullo, Fabrizia
Maggio, Roberta
Santini, Tiziana
Polverino, Federica
Biagioni, Stefano
Summa, Vincenzo
Toniatti, Carlo
Pasini, Diego
Stricker, Sigmar
Di Fabio, Romano
Chiacchiera, Fulvio
Peruzzi, Giovanna
Mozzetta, Chiara
author_sort Biferali, Beatrice
collection PubMed
description H3K9 methylation maintains cell identity orchestrating stable silencing and anchoring of alternate fate genes within the heterochromatic compartment underneath the nuclear lamina (NL). However, how cell type–specific genomic regions are specifically targeted to the NL is still elusive. Using fibro-adipogenic progenitors (FAPs) as a model, we identified Prdm16 as a nuclear envelope protein that anchors H3K9-methylated chromatin in a cell-specific manner. We show that Prdm16 mediates FAP developmental capacities by orchestrating lamina-associated domain organization and heterochromatin sequestration at the nuclear periphery. We found that Prdm16 localizes at the NL where it cooperates with the H3K9 methyltransferases G9a/GLP to mediate tethering and silencing of myogenic genes, thus repressing an alternative myogenic fate in FAPs. Genetic and pharmacological disruption of this repressive pathway confers to FAP myogenic competence, preventing fibro-adipogenic degeneration of dystrophic muscles. In summary, we reveal a druggable mechanism of heterochromatin perinuclear sequestration exploitable to reprogram FAPs in vivo.
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spelling pubmed-81721322021-06-10 Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair Biferali, Beatrice Bianconi, Valeria Perez, Daniel Fernandez Kronawitter, Sophie Pöhle Marullo, Fabrizia Maggio, Roberta Santini, Tiziana Polverino, Federica Biagioni, Stefano Summa, Vincenzo Toniatti, Carlo Pasini, Diego Stricker, Sigmar Di Fabio, Romano Chiacchiera, Fulvio Peruzzi, Giovanna Mozzetta, Chiara Sci Adv Research Articles H3K9 methylation maintains cell identity orchestrating stable silencing and anchoring of alternate fate genes within the heterochromatic compartment underneath the nuclear lamina (NL). However, how cell type–specific genomic regions are specifically targeted to the NL is still elusive. Using fibro-adipogenic progenitors (FAPs) as a model, we identified Prdm16 as a nuclear envelope protein that anchors H3K9-methylated chromatin in a cell-specific manner. We show that Prdm16 mediates FAP developmental capacities by orchestrating lamina-associated domain organization and heterochromatin sequestration at the nuclear periphery. We found that Prdm16 localizes at the NL where it cooperates with the H3K9 methyltransferases G9a/GLP to mediate tethering and silencing of myogenic genes, thus repressing an alternative myogenic fate in FAPs. Genetic and pharmacological disruption of this repressive pathway confers to FAP myogenic competence, preventing fibro-adipogenic degeneration of dystrophic muscles. In summary, we reveal a druggable mechanism of heterochromatin perinuclear sequestration exploitable to reprogram FAPs in vivo. American Association for the Advancement of Science 2021-06-02 /pmc/articles/PMC8172132/ /pubmed/34078594 http://dx.doi.org/10.1126/sciadv.abd9371 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Biferali, Beatrice
Bianconi, Valeria
Perez, Daniel Fernandez
Kronawitter, Sophie Pöhle
Marullo, Fabrizia
Maggio, Roberta
Santini, Tiziana
Polverino, Federica
Biagioni, Stefano
Summa, Vincenzo
Toniatti, Carlo
Pasini, Diego
Stricker, Sigmar
Di Fabio, Romano
Chiacchiera, Fulvio
Peruzzi, Giovanna
Mozzetta, Chiara
Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair
title Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair
title_full Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair
title_fullStr Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair
title_full_unstemmed Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair
title_short Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair
title_sort prdm16-mediated h3k9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172132/
https://www.ncbi.nlm.nih.gov/pubmed/34078594
http://dx.doi.org/10.1126/sciadv.abd9371
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