Journal
CELL STEM CELL
Volume 10, Issue 1, Pages 33-46Publisher
CELL PRESS
DOI: 10.1016/j.stem.2011.12.004
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Funding
- NYSTEM IDEA [C024285]
- ANR
- ERC
- MRC
- MRC Technology
- CRUK
- EMBO
- Grants-in-Aid for Scientific Research [23810035] Funding Source: KAKEN
- Biotechnology and Biological Sciences Research Council [BB/G011117/1] Funding Source: researchfish
- Medical Research Council [MC_U120036884, MC_U120085810] Funding Source: researchfish
- BBSRC [BB/G011117/1] Funding Source: UKRI
- MRC [MC_U120036884, MC_U120085810] Funding Source: UKRI
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The Polycomb Group (PcG) of chromatin modifiers regulates pluripotency and differentiation. Mammalian genomes encode multiple homologs of the Polycomb repressive complex 1 (PRC1) components, including five orthologs of the Drosophila Polycomb protein (Cbx2, Cbx4, Cbx6, Cbx7, and Cbx8). We have identified Cbx7 as the primary Polycomb ortholog of PRC1 complexes in embryonic stem cells (ESCs). The expression of Cbx7 is downregulated during ESC differentiation, preceding the upregulation of Cbx2, Cbx4, and Cbx8, which are directly repressed by Cbx7. Ectopic expression of Cbx7 inhibits differentiation and X chromosome inactivation and enhances ESC self-renewal. Conversely, Cbx7 knockdown induces differentiation and derepresses lineage-specific markers. In a functional screen, we identified the miR-125 and miR-181 families as regulators of Cbx7 that are induced during ESC differentiation. Ectopic expression of these miRNAs accelerates ESC differentiation via regulation of Cbx7. These observations establish a critical role for Cbx7 and its regulatory miRNAs in determining pluripotency.
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