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MicroRNA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation.

Ana O'Loghlen | Ana M Muñoz-Cabello | Alexandre Gaspar-Maia | Hsan-Au Wu | Ana Banito | Natalia Kunowska | Tomas Racek | Helen N Pemberton | Patrizia Beolchi | Fabrice Lavial | Osamu Masui | Michiel Vermeulen | Thomas Carroll | Johannes Graumann | Edith Heard | Niall Dillon | Veronique Azuara | Ambrosius P Snijders | Gordon Peters | Emily Bernstein | Jesus Gil
Cell stem cell | 2012

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.

Pubmed ID: 22226354

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/G011117/1
  • Agency: Medical Research Council, United Kingdom
    Id: MC_U120036884
  • Agency: Medical Research Council, United Kingdom
    Id: MC_U120085810
  • Agency: Worldwide Cancer Research, United Kingdom
    Id: 08-0118
  • Agency: Cancer Research UK, United Kingdom

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Knockout Mouse Project Repository (tool)

RRID:SCR_007318

Repository of mouse vectors, ES cells, mice, embryos, and sperm generated by NIH KOMP Mutagenesis Project. In addition, KOMP Repository offers services in support of KOMP products, including ES cell microinjection, vector cloning, post-insertional modification of cloned ES cells, cryopreservation, assisted reproduction techniques (IVF, ICSI) and mouse breeding, pathology services, phenotyping services, etc. KOMP Repository is final component of more than $50 million trans-NIH initiative to increase availability of genetically altered mice and related materials. The University of California, Davis (UC Davis) and Children''s Hospital Oakland Research Institute (CHORI) in Oakland, Calif., are collaborating to preserve, protect, and make available about 8,500 types of knockout mice and related products available to research community. Products are generated by two KOMP mutagenesis teams (CSD consortium and Regeneron Inc). All KOMP products generated by CSD consortium and Regeneron are available through KOMP Repository. Notice as of December 19, 2019: Materials from KOMP Repository have been deposited into MMRRC, including all mouse models and mouse embryonic stem cell lines. Eventually www.komp.org will be sunsetting, and IMSR will remove KOMP Repository listings, since they were double listed in MMRRC. MMRRC will contain the most accurate and up to date resource models.

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IMR-90 (tool)

RRID:CVCL_0347

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RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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HEK293T (tool)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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