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Nat Commun ; 12(1): 2829, 2021 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-33990559

RESUMEN

Polycomb group (PcG) proteins maintain cell identity by repressing gene expression during development. Surprisingly, emerging studies have recently reported that a number of PcG proteins directly activate gene expression during cell fate determination process. However, the mechanisms by which they direct gene activation in pluripotency remain poorly understood. Here, we show that Phc1, a subunit of canonical polycomb repressive complex 1 (cPRC1), can exert its function in pluripotency maintenance via a PRC1-independent activation of Nanog. Ablation of Phc1 reduces the expression of Nanog and overexpression of Nanog partially rescues impaired pluripotency caused by Phc1 depletion. We find that Phc1 interacts with Nanog and activates Nanog transcription by stabilizing the genome-wide chromatin interactions of the Nanog locus. This adds to the already known canonical function of PRC1 in pluripotency maintenance via a PRC1-dependent repression of differentiation genes. Overall, our study reveals a function of Phc1 to activate Nanog transcription through regulating chromatin architecture and proposes a paradigm for PcG proteins to maintain pluripotency.


Asunto(s)
Cromatina/genética , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/fisiología , Proteína Homeótica Nanog/genética , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/fisiología , Animales , Células Cultivadas , Técnicas de Silenciamiento del Gen , Técnicas de Inactivación de Genes , Genoma Humano , Células Madre Embrionarias Humanas/citología , Células Madre Embrionarias Humanas/fisiología , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Modelos Genéticos , Células Madre Embrionarias de Ratones/citología , Células Madre Embrionarias de Ratones/fisiología , Complejo Represivo Polycomb 1/antagonistas & inhibidores , Complejo Represivo Polycomb 1/deficiencia
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