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1.
J Biol Chem ; 287(49): 41103-17, 2012 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-23074223

RESUMEN

The nucleosome remodeling and deacetylation (NuRD) complex is required for modulating the transcription of essential pluripotency genes in ESC self-renewal. MBD3 is considered a key player in the formation of a functional NuRD complex. The recruitment of MBD3 to methylated promoters may require other prerequisite factors. We show that cyclin-dependent kinase 2-associated protein 1 (CDK2AP1), an essential gene for early embryonic development, plays a role in pluripotency of ESC by engaging MBD3 to the promoter region of Wnt signaling genes. The occupancy of MBD3 on several promoters of Wnt genes was significantly lost in the absence of CDK2AP1, resulting in hyperactivation of Wnt. We propose that the transcriptional modulation of the Wnt pathway mediated by NuRD requires the presence of essential auxiliary components such as CDK2AP1, which may aid the association of the complex with specific focal regions of the target promoters.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Células Madre Embrionarias/citología , Nucleosomas/metabolismo , Proteínas Quinasas/metabolismo , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteínas Wnt/metabolismo , Animales , Metilación de ADN , Epigénesis Genética , Eliminación de Gen , Perfilación de la Expresión Génica , Ratones , Modelos Biológicos , Modelos Genéticos , Fenotipo , Regiones Promotoras Genéticas , Transducción de Señal , Células Madre/citología , Transcripción Genética
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