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MicroRNA Regulation of Cbx7 Mediates a Switch of Polycomb Orthologs during ESC Differentiation

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 ident...

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Autores principales: O'Loghlen, Ana, Muñoz-Cabello, Ana M., Gaspar-Maia, Alexandre, Wu, Hsan-Au, Banito, Ana, Kunowska, Natalia, Racek, Tomas, Pemberton, Helen N., Beolchi, Patrizia, Lavial, Fabrice, Masui, Osamu, Vermeulen, Michiel, Carroll, Thomas, Graumann, Johannes, Heard, Edith, Dillon, Niall, Azuara, Veronique, Snijders, Ambrosius P., Peters, Gordon, Bernstein, Emily, Gil, Jesus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277884/
https://www.ncbi.nlm.nih.gov/pubmed/22226354
http://dx.doi.org/10.1016/j.stem.2011.12.004
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author O'Loghlen, Ana
Muñoz-Cabello, Ana M.
Gaspar-Maia, Alexandre
Wu, Hsan-Au
Banito, Ana
Kunowska, Natalia
Racek, Tomas
Pemberton, Helen N.
Beolchi, Patrizia
Lavial, Fabrice
Masui, Osamu
Vermeulen, Michiel
Carroll, Thomas
Graumann, Johannes
Heard, Edith
Dillon, Niall
Azuara, Veronique
Snijders, Ambrosius P.
Peters, Gordon
Bernstein, Emily
Gil, Jesus
author_facet O'Loghlen, Ana
Muñoz-Cabello, Ana M.
Gaspar-Maia, Alexandre
Wu, Hsan-Au
Banito, Ana
Kunowska, Natalia
Racek, Tomas
Pemberton, Helen N.
Beolchi, Patrizia
Lavial, Fabrice
Masui, Osamu
Vermeulen, Michiel
Carroll, Thomas
Graumann, Johannes
Heard, Edith
Dillon, Niall
Azuara, Veronique
Snijders, Ambrosius P.
Peters, Gordon
Bernstein, Emily
Gil, Jesus
author_sort O'Loghlen, Ana
collection PubMed
description 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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spelling pubmed-32778842012-02-24 MicroRNA Regulation of Cbx7 Mediates a Switch of Polycomb Orthologs during ESC Differentiation O'Loghlen, Ana Muñoz-Cabello, Ana M. Gaspar-Maia, Alexandre Wu, Hsan-Au Banito, Ana Kunowska, Natalia Racek, Tomas Pemberton, Helen N. Beolchi, Patrizia Lavial, Fabrice Masui, Osamu Vermeulen, Michiel Carroll, Thomas Graumann, Johannes Heard, Edith Dillon, Niall Azuara, Veronique Snijders, Ambrosius P. Peters, Gordon Bernstein, Emily Gil, Jesus Cell Stem Cell Article 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. Cell Press 2012-01-06 /pmc/articles/PMC3277884/ /pubmed/22226354 http://dx.doi.org/10.1016/j.stem.2011.12.004 Text en © 2012 ELL & Excerpta Medica. https://creativecommons.org/licenses/by/4.0/ Open Access under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) license
spellingShingle Article
O'Loghlen, Ana
Muñoz-Cabello, Ana M.
Gaspar-Maia, Alexandre
Wu, Hsan-Au
Banito, Ana
Kunowska, Natalia
Racek, Tomas
Pemberton, Helen N.
Beolchi, Patrizia
Lavial, Fabrice
Masui, Osamu
Vermeulen, Michiel
Carroll, Thomas
Graumann, Johannes
Heard, Edith
Dillon, Niall
Azuara, Veronique
Snijders, Ambrosius P.
Peters, Gordon
Bernstein, Emily
Gil, Jesus
MicroRNA Regulation of Cbx7 Mediates a Switch of Polycomb Orthologs during ESC Differentiation
title MicroRNA Regulation of Cbx7 Mediates a Switch of Polycomb Orthologs during ESC Differentiation
title_full MicroRNA Regulation of Cbx7 Mediates a Switch of Polycomb Orthologs during ESC Differentiation
title_fullStr MicroRNA Regulation of Cbx7 Mediates a Switch of Polycomb Orthologs during ESC Differentiation
title_full_unstemmed MicroRNA Regulation of Cbx7 Mediates a Switch of Polycomb Orthologs during ESC Differentiation
title_short MicroRNA Regulation of Cbx7 Mediates a Switch of Polycomb Orthologs during ESC Differentiation
title_sort microrna regulation of cbx7 mediates a switch of polycomb orthologs during esc differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277884/
https://www.ncbi.nlm.nih.gov/pubmed/22226354
http://dx.doi.org/10.1016/j.stem.2011.12.004
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