Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/223994
Chromatin activity of IκBα mediates the exit from naïve pluripotency
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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.
Matèries
Matèries (anglès)
Citació
Citació
PALMA, Luis g., ALVAREZ-VILLANUEVA, Daniel, MAQUEDA, Maria, BARRERO, Mercedes, IGLESIAS, Arnau, BERTRAN, Joan, 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. _eLife_. 2025. Vol. 14. [consulta: 24 de gener de 2026]. ISSN: 2050-084X. [Disponible a: https://hdl.handle.net/2445/223994]