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Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators

Item Type:Article
Title:Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators
Creators Name:Landeira, D. and Sauer, S. and Poot, R. and Dvorkina, M. and Mazzarella, L. and Jorgensen, H.F. and Pereira, C.F. and Leleu, M. and Piccolo, F.M. and Spivakov, M. and Brookes, E. and Pombo, A. and Fisher, C. and Skarnes, W.C. and Snoek, T. and Bezstarosti, K. and Demmers, J. and Klose, R.J. and Casanova, M. and Tavares, L. and Brockdorff, N. and Merkenschlager, M. and Fisher, A.G.
Abstract:Polycomb Repressor Complexes (PRCs) are important regulators of embryogenesis. In embryonic stem (ES) cells many genes that regulate subsequent stages in development are enriched at their promoters for PRC1, PRC2 and Ser 5-phosphorylated RNA Polymerase II (RNAP), and contain domains of 'bivalent' chromatin (enriched for H3K4me3; histone H3 di- or trimethylated at Lys 4 and H3K27me3; histone H3 trimethylated at Lys 27). Loss of individual PRC components in ES cells can lead to gene de-repression and to unscheduled differentiation. Here we show that Jarid2 is a novel subunit of PRC2 that is required for the co-recruitment of PRC1 and RNAP to genes that regulate development in ES cells. Jarid2-deficient ES cells showed reduced H3K4me2/me3 and H3K27me3 marking and PRC1/PRC2 recruitment, and did not efficiently establish Ser 5-phosporylated RNAP at target genes. ES cells lacking Jarid2, in contrast to previously characterized PRC1 and PRC2 mutants, did not inappropriately express PRC2 target genes. Instead, they show a severely compromised capacity for successful differentiation towards neural or mesodermal fates and failed to correctly initiate lineage-specific gene expression in vitro. Collectively, these data indicate that transcriptional priming of bivalent genes in pluripotent ES cells is Jarid2-dependent, and suggests that priming is critical for subsequent multi-lineage differentiation.
Keywords:Cell Differentiation, Chromatin, Embryonic Stem Cells, Histones, Pluripotent Stem Cells, Proteins, RNA Polymerase II
Source:Nature Cell Biology
ISSN:1465-7392
Publisher:Nature Publishing Group (U.K.)
Volume:12
Number:6
Page Range:618-624
Date:June 2010
Official Publication:https://doi.org/10.1038/ncb2065
PubMed:View item in PubMed

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