Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros




Base de datos
Intervalo de año de publicación
1.
Nucleic Acids Res ; 52(12): 7063-7080, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38808662

RESUMEN

Cohesin plays a crucial role in the organization of topologically-associated domains (TADs), which influence gene expression and DNA replication timing. Whether epigenetic regulators may affect TADs via cohesin to mediate DNA replication remains elusive. Here, we discover that the histone demethylase PHF2 associates with RAD21, a core subunit of cohesin, to regulate DNA replication in mouse neural stem cells (NSC). PHF2 loss impairs DNA replication due to the activation of dormant replication origins in NSC. Notably, the PHF2/RAD21 co-bound genomic regions are characterized by CTCF enrichment and epigenomic features that resemble efficient, active replication origins, and can act as boundaries to separate adjacent domains. Accordingly, PHF2 loss weakens TADs and chromatin loops at the co-bound loci due to reduced RAD21 occupancy. The observed topological and DNA replication defects in PHF2 KO NSC support a cohesin-dependent mechanism. Furthermore, we demonstrate that the PHF2/RAD21 complex exerts little effect on gene regulation, and that PHF2's histone-demethylase activity is dispensable for normal DNA replication and proliferation of NSC. We propose that PHF2 may serve as a topological accessory to cohesin for cohesin localization to TADs and chromatin loops, where cohesin represses dormant replication origins directly or indirectly, to sustain DNA replication in NSC.


Asunto(s)
Proteínas de Ciclo Celular , Proteínas Cromosómicas no Histona , Cohesinas , Replicación del ADN , Proteínas de Unión al ADN , Células-Madre Neurales , Animales , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Ratones , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Cromatina/metabolismo , Origen de Réplica , Histona Demetilasas/metabolismo , Histona Demetilasas/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Genoma/genética , Factor de Unión a CCCTC/metabolismo , Factor de Unión a CCCTC/genética , Ratones Noqueados
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA