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Publication : PHC1 maintains pluripotency by organizing genome-wide chromatin interactions of the Nanog locus.

First Author  Chen L Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  2829
PubMed ID  33990559 Mgi Jnum  J:306096
Mgi Id  MGI:6713869 Doi  10.1038/s41467-021-22871-0
Citation  Chen L, et al. (2021) PHC1 maintains pluripotency by organizing genome-wide chromatin interactions of the Nanog locus. Nat Commun 12(1):2829
abstractText  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.
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