期刊
STEM CELL REPORTS
卷 17, 期 5, 页码 1198-1214出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2022.02.020
关键词
-
资金
- National Natu-ral Science Foundation of China [31970810]
Polycomb group proteins form PRC1 subcomplexes that play a crucial role in cell fate determination during embryonic development. Non-canonical PRC1 is essential for maintaining ESC pluripotency, and there is functional redundancy between non-canonical and canonical PRC1. These findings highlight the importance of PRC1 subcomplexes in silencing lineage-specific genes and ensuring robust maintenance of ESC identity.
Polycomb group proteins assemble into multi-protein complexes, known as Polycomb repressive complexes 1 and 2 (PRC1 and PRC2), that guide cell fate decisions during embryonic development. PRC1 forms an array of biochemically distinct canonical PRC1 (cPRC1) or non-canonical PRC1 (ncPRC1) complexes characterized by the mutually exclusive presence of PCGF (PCGF1-PCGF6) paralog subunit; however, whether each one of these subcomplexes fulfills a distinct role remains largely controversial. Here, by performing a CRISPRbased loss-of-function screen in embryonic stem cells (ESCs), we uncovered a previously unappreciated functional redundancy among PRC1 subcomplexes. Disruption of ncPRC1, but not cPRC1, displayed severe defects in ESC pluripotency. Remarkably, coablation of non-canonical and canonical PRC1 in ESCs resulted in exacerbation of the phenotype observed in the non-canonical PRC1-null ESCs, highlighting the importance of functional redundancy among PRC1 subcomplexes. Together, our studies demonstrate that PRC1 subcomplexes act redundantly to silence lineage-specific genes and ensure robust maintenance of ESC identity.
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