Article (Scientific journals)
A Cbx8-containing polycomb complex facilitates the transition to gene activation during ES cell differentiation.
Creppe, Catherine; Palau, Ana; Malinverni, Roberto et al.
2014In PLoS Genetics, 10 (12), p. 1004851
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Keywords :
Animals; Cell Differentiation; Cells, Cultured; Chromatin/genetics/metabolism; Chromatin Immunoprecipitation; Embryonic Stem Cells/cytology/metabolism; Gene Deletion; Histones/genetics/metabolism; Mice; Polycomb Repressive Complex 1/genetics/metabolism; Polycomb-Group Proteins/genetics/metabolism; Protein Binding; Proteomics; Transcriptional Activation; Ubiquitins/genetics/metabolism; Up-Regulation
Abstract :
[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Creppe, Catherine  ;  Université de Liège > Giga - Neurosciences
Palau, Ana 
Malinverni, Roberto
Valero, Vanesa
Buschbeck, Marcus
 These authors have contributed equally to this work.
Language :
English
Title :
A Cbx8-containing polycomb complex facilitates the transition to gene activation during ES cell differentiation.
Publication date :
11 December 2014
Journal title :
PLoS Genetics
ISSN :
1553-7390
eISSN :
1553-7404
Publisher :
Public Library of Science, United States - California
Volume :
10
Issue :
12
Pages :
e1004851
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 26 January 2016

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