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Nature ; 618(7963): 180-187, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37225980

RESUMEN

For cells to initiate and sustain a differentiated state, it is necessary that a 'memory' of this state is transmitted through mitosis to the daughter cells1-3. Mammalian switch/sucrose non-fermentable (SWI/SNF) complexes (also known as Brg1/Brg-associated factors, or BAF) control cell identity by modulating chromatin architecture to regulate gene expression4-7, but whether they participate in cell fate memory is unclear. Here we provide evidence that subunits of SWI/SNF act as mitotic bookmarks to safeguard cell identity during cell division. The SWI/SNF core subunits SMARCE1 and SMARCB1 are displaced from enhancers but are bound to promoters during mitosis, and we show that this binding is required for appropriate reactivation of bound genes after mitotic exit. Ablation of SMARCE1 during a single mitosis in mouse embryonic stem cells is sufficient to disrupt gene expression, impair the occupancy of several established bookmarks at a subset of their targets and cause aberrant neural differentiation. Thus, SWI/SNF subunit SMARCE1 has a mitotic bookmarking role and is essential for heritable epigenetic fidelity during transcriptional reprogramming.


Asunto(s)
Diferenciación Celular , Proteínas Cromosómicas no Histona , Epigénesis Genética , Mitosis , Animales , Ratones , Diferenciación Celular/genética , Cromatina/genética , Ensamble y Desensamble de Cromatina/genética , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Mitosis/genética , Proteínas Cromosómicas no Histona/deficiencia , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Subunidades de Proteína/metabolismo , Células Madre Embrionarias de Ratones/metabolismo , Elementos de Facilitación Genéticos/genética , Regiones Promotoras Genéticas/genética , División Celular/genética , Epigénesis Genética/genética
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