Chromatin activity of IκBα mediates the exit from naïve pluripotency

Palma, Luis G.; Alvarez-Villanueva, Daniel; Maqueda, Maria; Barrero, Mercedes; Iglesias, Arnau; Bertran, Joan, 1964-; Alvarez, Damiana; García Prieto, Carlos Antonio; Ballare, Cecilia; Esteller, Manel; Rodríguez Cortez, Virginia Carolina; Bueno, Clara; Vidal-Bel, August; Villanueva Garatachea, Alberto; Menéndez, Pablo; Stik, Gregoire; Croce, Luciano Di; Payer, Bernhard; Espinosa, Lluís; Bigas Salvans, Anna

Chromatin activity of IκBα mediates the exit from naïve pluripotency

Maintenance of pluripotency is a multifactorial process in which NF-κB is a negative regulator. Our previous work identified a chromatin role for IκBα, the master regulator of NF-κB signaling, that is critical for the proper regulation of various tissue stem cells. Here, we found that IκBα accumulat...

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Detalles Bibliográficos
Autores:	Palma, Luis G., Alvarez-Villanueva, Daniel, Maqueda, Maria, Barrero, Mercedes, Iglesias, Arnau, Bertran, Joan, 1964-, Alvarez, Damiana, García Prieto, Carlos Antonio, Ballare, Cecilia, Esteller, Manel, Rodríguez Cortez, Virginia Carolina, Bueno, Clara, Vidal-Bel, August, Villanueva Garatachea, Alberto, Menéndez, Pablo, Stik, Gregoire, Croce, Luciano Di, Payer, Bernhard, Espinosa, Lluís, Bigas Salvans, Anna
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2025
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/223994
Acceso en línea:	https://hdl.handle.net/2445/223994
Access Level:	acceso abierto
Palabra clave:	Animals Diferenciació cel·lular Cromatina Epigènesi Cell diferentiation Chromatin Epigenesis

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spelling	Chromatin activity of IκBα mediates the exit from naïve pluripotencyPalma, Luis G.Alvarez-Villanueva, DanielMaqueda, MariaBarrero, MercedesIglesias, ArnauBertran, Joan, 1964-Alvarez, DamianaGarcía Prieto, Carlos AntonioBallare, CeciliaEsteller, ManelRodríguez Cortez, Virginia CarolinaBueno, ClaraVidal-Bel, AugustVillanueva Garatachea, AlbertoMenéndez, PabloStik, GregoireCroce, Luciano DiPayer, BernhardEspinosa, LluísBigas Salvans, AnnaAnimalsDiferenciació cel·lularCromatinaEpigènesiAnimalsCell diferentiationChromatinEpigenesisMaintenance of pluripotency is a multifactorial process in which NF-κB is a negative regulator. Our previous work identified a chromatin role for IκBα, the master regulator of NF-κB signaling, that is critical for the proper regulation of various tissue stem cells. Here, we found that IκBα accumulates specifically in the chromatin fraction of mouse pluripotent stem cells. IκBα depletion does not affect NF-kB-dependent transcription, but causes a profound epigenetic rewiring in pluripotent stem cells, including alterations in H3K27me3, a histone mark catalyzed by Polycomb repression complex 2. Chromatin changes induced by IκBα depletion affect a subset of pluripotency genes and are associated with altered gene transcription. At the cellular level, IκBα-deficient embryonic stem cells are arrested in a naive pluripotency state when cultured in serum/LIF conditions and fail to exit pluripotency under differentiation conditions. By constructing separation-of-function mutants, we show that the effects of IκBα in regulating stem cell pluripotency are NF-κB-independent, but mainly rely on its chromatin-related function. Taken together, our results reveal a novel mechanism by which IκBα participates in the regulation of the pluripotent state of mouse embryonic stem cells and shed light on the interplay between inflammatory signals and the regulation of pluripotency.eLife Sciences2025202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion24 p.application/pdfhttps://hdl.handle.net/2445/223994Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.7554/eLife.102784eLife, 2025, vol. 14https://doi.org/10.7554/eLife.102784cc-by (c) Palma, L.G. et al., 2025http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2239942026-05-29T05:05:01Z
dc.title.none.fl_str_mv	Chromatin activity of IκBα mediates the exit from naïve pluripotency
title	Chromatin activity of IκBα mediates the exit from naïve pluripotency
spellingShingle	Chromatin activity of IκBα mediates the exit from naïve pluripotency Palma, Luis G. Animals Diferenciació cel·lular Cromatina Epigènesi Animals Cell diferentiation Chromatin Epigenesis
title_short	Chromatin activity of IκBα mediates the exit from naïve pluripotency
title_full	Chromatin activity of IκBα mediates the exit from naïve pluripotency
title_fullStr	Chromatin activity of IκBα mediates the exit from naïve pluripotency
title_full_unstemmed	Chromatin activity of IκBα mediates the exit from naïve pluripotency
title_sort	Chromatin activity of IκBα mediates the exit from naïve pluripotency
dc.creator.none.fl_str_mv	Palma, Luis G. Alvarez-Villanueva, Daniel Maqueda, Maria Barrero, Mercedes Iglesias, Arnau Bertran, Joan, 1964- Alvarez, Damiana García Prieto, Carlos Antonio Ballare, Cecilia Esteller, Manel Rodríguez Cortez, Virginia Carolina Bueno, Clara Vidal-Bel, August Villanueva Garatachea, Alberto Menéndez, Pablo Stik, Gregoire Croce, Luciano Di Payer, Bernhard Espinosa, Lluís Bigas Salvans, Anna
author	Palma, Luis G.
author_facet	Palma, Luis G. Alvarez-Villanueva, Daniel Maqueda, Maria Barrero, Mercedes Iglesias, Arnau Bertran, Joan, 1964- Alvarez, Damiana García Prieto, Carlos Antonio Ballare, Cecilia Esteller, Manel Rodríguez Cortez, Virginia Carolina Bueno, Clara Vidal-Bel, August Villanueva Garatachea, Alberto Menéndez, Pablo Stik, Gregoire Croce, Luciano Di Payer, Bernhard Espinosa, Lluís Bigas Salvans, Anna
author_role	author
author2	Alvarez-Villanueva, Daniel Maqueda, Maria Barrero, Mercedes Iglesias, Arnau Bertran, Joan, 1964- Alvarez, Damiana García Prieto, Carlos Antonio Ballare, Cecilia Esteller, Manel Rodríguez Cortez, Virginia Carolina Bueno, Clara Vidal-Bel, August Villanueva Garatachea, Alberto Menéndez, Pablo Stik, Gregoire Croce, Luciano Di Payer, Bernhard Espinosa, Lluís Bigas Salvans, Anna
author2_role	author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Animals Diferenciació cel·lular Cromatina Epigènesi Animals Cell diferentiation Chromatin Epigenesis
topic	Animals Diferenciació cel·lular Cromatina Epigènesi Animals Cell diferentiation Chromatin Epigenesis
description	Maintenance of pluripotency is a multifactorial process in which NF-κB is a negative regulator. Our previous work identified a chromatin role for IκBα, the master regulator of NF-κB signaling, that is critical for the proper regulation of various tissue stem cells. Here, we found that IκBα accumulates specifically in the chromatin fraction of mouse pluripotent stem cells. IκBα depletion does not affect NF-kB-dependent transcription, but causes a profound epigenetic rewiring in pluripotent stem cells, including alterations in H3K27me3, a histone mark catalyzed by Polycomb repression complex 2. Chromatin changes induced by IκBα depletion affect a subset of pluripotency genes and are associated with altered gene transcription. At the cellular level, IκBα-deficient embryonic stem cells are arrested in a naive pluripotency state when cultured in serum/LIF conditions and fail to exit pluripotency under differentiation conditions. By constructing separation-of-function mutants, we show that the effects of IκBα in regulating stem cell pluripotency are NF-κB-independent, but mainly rely on its chromatin-related function. Taken together, our results reveal a novel mechanism by which IκBα participates in the regulation of the pluripotent state of mouse embryonic stem cells and shed light on the interplay between inflammatory signals and the regulation of pluripotency.
publishDate	2025
dc.date.none.fl_str_mv	2025 2025 2025 2025
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/223994
url	https://hdl.handle.net/2445/223994
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.7554/eLife.102784 eLife, 2025, vol. 14 https://doi.org/10.7554/eLife.102784
dc.rights.none.fl_str_mv	cc-by (c) Palma, L.G. et al., 2025 http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by (c) Palma, L.G. et al., 2025 http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	24 p. application/pdf
dc.publisher.none.fl_str_mv	eLife Sciences
publisher.none.fl_str_mv	eLife Sciences
dc.source.none.fl_str_mv	Articles publicats en revistes (Ciències Fisiològiques) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,812429

Chromatin activity of IκBα mediates the exit from naïve pluripotency

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