Cargando…

A Cbx8-Containing Polycomb Complex Facilitates the Transition to Gene Activation during ES Cell Differentiation

Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Our project aimed to identify Cbx8 binding sites in...

Descripción completa

Detalles Bibliográficos
Autores principales: Creppe, Catherine, Palau, Anna, Malinverni, Roberto, Valero, Vanesa, Buschbeck, Marcus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263398/
https://www.ncbi.nlm.nih.gov/pubmed/25500566
http://dx.doi.org/10.1371/journal.pgen.1004851
_version_ 1782348562201313280
author Creppe, Catherine
Palau, Anna
Malinverni, Roberto
Valero, Vanesa
Buschbeck, Marcus
author_facet Creppe, Catherine
Palau, Anna
Malinverni, Roberto
Valero, Vanesa
Buschbeck, Marcus
author_sort Creppe, Catherine
collection PubMed
description Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Our project aimed to identify Cbx8 binding sites in differentiating mouse embryonic stem cells. Therefore, we used a genome-wide chromatin immunoprecipitation of endogenous Cbx8 coupled to direct massive parallel sequencing (ChIP-Seq). Our analysis identified 171 high confidence peaks. By crossing our data with previously published microarray analysis, we show that several differentiation genes transiently recruit Cbx8 during their early activation. Depletion of Cbx8 partially impairs the transcriptional activation of these genes. Both interaction analysis, as well as chromatin immunoprecipitation experiments support the idea that activating Cbx8 acts in the context of an intact PRC1 complex. Prolonged gene activation results in eviction of PRC1 despite persisting H3K27me3 and H2A ubiquitination. The composition of PRC1 is highly modular and changes when embryonic stem cells commit to differentiation. We further demonstrate that the exchange of Cbx7 for Cbx8 is required for the effective activation of differentiation genes. Taken together, our results establish a function for a Cbx8-containing complex in facilitating the transition from a Polycomb-repressed chromatin state to an active state. As this affects several key regulatory differentiation genes this mechanism is likely to contribute to the robust execution of differentiation programs.
format Online
Article
Text
id pubmed-4263398
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-42633982014-12-19 A Cbx8-Containing Polycomb Complex Facilitates the Transition to Gene Activation during ES Cell Differentiation Creppe, Catherine Palau, Anna Malinverni, Roberto Valero, Vanesa Buschbeck, Marcus PLoS Genet Research Article Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Our project aimed to identify Cbx8 binding sites in differentiating mouse embryonic stem cells. Therefore, we used a genome-wide chromatin immunoprecipitation of endogenous Cbx8 coupled to direct massive parallel sequencing (ChIP-Seq). Our analysis identified 171 high confidence peaks. By crossing our data with previously published microarray analysis, we show that several differentiation genes transiently recruit Cbx8 during their early activation. Depletion of Cbx8 partially impairs the transcriptional activation of these genes. Both interaction analysis, as well as chromatin immunoprecipitation experiments support the idea that activating Cbx8 acts in the context of an intact PRC1 complex. Prolonged gene activation results in eviction of PRC1 despite persisting H3K27me3 and H2A ubiquitination. The composition of PRC1 is highly modular and changes when embryonic stem cells commit to differentiation. We further demonstrate that the exchange of Cbx7 for Cbx8 is required for the effective activation of differentiation genes. Taken together, our results establish a function for a Cbx8-containing complex in facilitating the transition from a Polycomb-repressed chromatin state to an active state. As this affects several key regulatory differentiation genes this mechanism is likely to contribute to the robust execution of differentiation programs. Public Library of Science 2014-12-11 /pmc/articles/PMC4263398/ /pubmed/25500566 http://dx.doi.org/10.1371/journal.pgen.1004851 Text en © 2014 Creppe 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
Creppe, Catherine
Palau, Anna
Malinverni, Roberto
Valero, Vanesa
Buschbeck, Marcus
A Cbx8-Containing Polycomb Complex Facilitates the Transition to Gene Activation during ES Cell Differentiation
title A Cbx8-Containing Polycomb Complex Facilitates the Transition to Gene Activation during ES Cell Differentiation
title_full A Cbx8-Containing Polycomb Complex Facilitates the Transition to Gene Activation during ES Cell Differentiation
title_fullStr A Cbx8-Containing Polycomb Complex Facilitates the Transition to Gene Activation during ES Cell Differentiation
title_full_unstemmed A Cbx8-Containing Polycomb Complex Facilitates the Transition to Gene Activation during ES Cell Differentiation
title_short A Cbx8-Containing Polycomb Complex Facilitates the Transition to Gene Activation during ES Cell Differentiation
title_sort cbx8-containing polycomb complex facilitates the transition to gene activation during es cell differentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263398/
https://www.ncbi.nlm.nih.gov/pubmed/25500566
http://dx.doi.org/10.1371/journal.pgen.1004851
work_keys_str_mv AT creppecatherine acbx8containingpolycombcomplexfacilitatesthetransitiontogeneactivationduringescelldifferentiation
AT palauanna acbx8containingpolycombcomplexfacilitatesthetransitiontogeneactivationduringescelldifferentiation
AT malinverniroberto acbx8containingpolycombcomplexfacilitatesthetransitiontogeneactivationduringescelldifferentiation
AT valerovanesa acbx8containingpolycombcomplexfacilitatesthetransitiontogeneactivationduringescelldifferentiation
AT buschbeckmarcus acbx8containingpolycombcomplexfacilitatesthetransitiontogeneactivationduringescelldifferentiation
AT creppecatherine cbx8containingpolycombcomplexfacilitatesthetransitiontogeneactivationduringescelldifferentiation
AT palauanna cbx8containingpolycombcomplexfacilitatesthetransitiontogeneactivationduringescelldifferentiation
AT malinverniroberto cbx8containingpolycombcomplexfacilitatesthetransitiontogeneactivationduringescelldifferentiation
AT valerovanesa cbx8containingpolycombcomplexfacilitatesthetransitiontogeneactivationduringescelldifferentiation
AT buschbeckmarcus cbx8containingpolycombcomplexfacilitatesthetransitiontogeneactivationduringescelldifferentiation