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CAF-1 Is Essential for Heterochromatin Organization in Pluripotent Embryonic Cells

During mammalian development, chromatin dynamics and epigenetic marking are important for genome reprogramming. Recent data suggest an important role for the chromatin assembly machinery in this process. To analyze the role of chromatin assembly factor 1 (CAF-1) during pre-implantation development,...

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Autores principales: Houlard, Martin, Berlivet, Soizik, Probst, Aline V, Quivy, Jean-Pierre, Héry, Patrick, Almouzni, Geneviève, Gérard, Matthieu
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1630711/
https://www.ncbi.nlm.nih.gov/pubmed/17083276
http://dx.doi.org/10.1371/journal.pgen.0020181
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author Houlard, Martin
Berlivet, Soizik
Probst, Aline V
Quivy, Jean-Pierre
Héry, Patrick
Almouzni, Geneviève
Gérard, Matthieu
author_facet Houlard, Martin
Berlivet, Soizik
Probst, Aline V
Quivy, Jean-Pierre
Héry, Patrick
Almouzni, Geneviève
Gérard, Matthieu
author_sort Houlard, Martin
collection PubMed
description During mammalian development, chromatin dynamics and epigenetic marking are important for genome reprogramming. Recent data suggest an important role for the chromatin assembly machinery in this process. To analyze the role of chromatin assembly factor 1 (CAF-1) during pre-implantation development, we generated a mouse line carrying a targeted mutation in the gene encoding its large subunit, p150CAF-1. Loss of p150CAF-1 in homozygous mutants leads to developmental arrest at the 16-cell stage. Absence of p150CAF-1 in these embryos results in severe alterations in the nuclear organization of constitutive heterochromatin. We provide evidence that in wild-type embryos, heterochromatin domains are extensively reorganized between the two-cell and blastocyst stages. In p150CAF-1 mutant 16-cell stage embryos, the altered organization of heterochromatin displays similarities to the structure of heterochromatin in two- to four-cell stage wild-type embryos, suggesting that CAF-1 is required for the maturation of heterochromatin during preimplantation development. In embryonic stem cells, depletion of p150CAF-1 using RNA interference results in the mislocalization, loss of clustering, and decondensation of pericentric heterochromatin domains. Furthermore, loss of CAF-1 in these cells results in the alteration of epigenetic histone methylation marks at the level of pericentric heterochromatin. These alterations of heterochromatin are not found in p150CAF-1-depleted mouse embryonic fibroblasts, which are cells that are already lineage committed, suggesting that CAF-1 is specifically required for heterochromatin organization in pluripotent embryonic cells. Our findings underline the role of the chromatin assembly machinery in controlling the spatial organization and epigenetic marking of the genome in early embryos and embryonic stem cells.
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spelling pubmed-16307112006-11-29 CAF-1 Is Essential for Heterochromatin Organization in Pluripotent Embryonic Cells Houlard, Martin Berlivet, Soizik Probst, Aline V Quivy, Jean-Pierre Héry, Patrick Almouzni, Geneviève Gérard, Matthieu PLoS Genet Research Article During mammalian development, chromatin dynamics and epigenetic marking are important for genome reprogramming. Recent data suggest an important role for the chromatin assembly machinery in this process. To analyze the role of chromatin assembly factor 1 (CAF-1) during pre-implantation development, we generated a mouse line carrying a targeted mutation in the gene encoding its large subunit, p150CAF-1. Loss of p150CAF-1 in homozygous mutants leads to developmental arrest at the 16-cell stage. Absence of p150CAF-1 in these embryos results in severe alterations in the nuclear organization of constitutive heterochromatin. We provide evidence that in wild-type embryos, heterochromatin domains are extensively reorganized between the two-cell and blastocyst stages. In p150CAF-1 mutant 16-cell stage embryos, the altered organization of heterochromatin displays similarities to the structure of heterochromatin in two- to four-cell stage wild-type embryos, suggesting that CAF-1 is required for the maturation of heterochromatin during preimplantation development. In embryonic stem cells, depletion of p150CAF-1 using RNA interference results in the mislocalization, loss of clustering, and decondensation of pericentric heterochromatin domains. Furthermore, loss of CAF-1 in these cells results in the alteration of epigenetic histone methylation marks at the level of pericentric heterochromatin. These alterations of heterochromatin are not found in p150CAF-1-depleted mouse embryonic fibroblasts, which are cells that are already lineage committed, suggesting that CAF-1 is specifically required for heterochromatin organization in pluripotent embryonic cells. Our findings underline the role of the chromatin assembly machinery in controlling the spatial organization and epigenetic marking of the genome in early embryos and embryonic stem cells. Public Library of Science 2006-11 2006-11-03 /pmc/articles/PMC1630711/ /pubmed/17083276 http://dx.doi.org/10.1371/journal.pgen.0020181 Text en © 2006 Houlard et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Houlard, Martin
Berlivet, Soizik
Probst, Aline V
Quivy, Jean-Pierre
Héry, Patrick
Almouzni, Geneviève
Gérard, Matthieu
CAF-1 Is Essential for Heterochromatin Organization in Pluripotent Embryonic Cells
title CAF-1 Is Essential for Heterochromatin Organization in Pluripotent Embryonic Cells
title_full CAF-1 Is Essential for Heterochromatin Organization in Pluripotent Embryonic Cells
title_fullStr CAF-1 Is Essential for Heterochromatin Organization in Pluripotent Embryonic Cells
title_full_unstemmed CAF-1 Is Essential for Heterochromatin Organization in Pluripotent Embryonic Cells
title_short CAF-1 Is Essential for Heterochromatin Organization in Pluripotent Embryonic Cells
title_sort caf-1 is essential for heterochromatin organization in pluripotent embryonic cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1630711/
https://www.ncbi.nlm.nih.gov/pubmed/17083276
http://dx.doi.org/10.1371/journal.pgen.0020181
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