PHC1 maintains pluripotency by organizing genome-wide chromatin interactions of the Nanog locus
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 d...
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Veröffentlicht in: | Nature communications 2021-05, Vol.12 (1), p.2829-2829, Article 2829 |
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Sprache: | eng |
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Zusammenfassung: | 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.
Phc1 is a subunit of the polycomb repressive complex 1 (PRC1), which represses gene expression during development. Here the authors show that Phc1 acts independently from PRC1 to activate Nanog transcription by stabilizing genome-wide chromatin interactions of the Nanog locus, and in turn stabilize pluripotency. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-021-22871-0 |