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 BernsteinJesus Gil

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)33-46
Number of pages14
JournalCell Stem Cell
Volume10
Issue number1
DOIs
StatePublished - Jan 6 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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