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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

Landeira, David; Sauer, Stephan P A; Poot, Raymond; Dvorkina, Maria; Mazzarella, Luca; Jørgensen, Helle F.; Pereira, C. Filipe LU ; Leleu, Marion; Piccolo, Francesco M. and Spivakov, Mikhail, et al. (2010) In Nature Cell Biology 12(6). p.618-624
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... (More)

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.

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Nature Cell Biology
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12
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7 pages
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  • scopus:77953120646
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1465-7392
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10.1038/ncb2065
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English
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ba1dbea1-04b1-41bd-a836-3142f1f27ea9
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572404/pdf/emss-51599.pdf
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2017-10-02 17:30:25
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@article{ba1dbea1-04b1-41bd-a836-3142f1f27ea9,
  abstract     = {<p>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.</p>},
  author       = {Landeira, David and Sauer, Stephan P A and Poot, Raymond and Dvorkina, Maria and Mazzarella, Luca and Jørgensen, Helle F. and Pereira, C. Filipe and Leleu, Marion and Piccolo, Francesco M. and Spivakov, Mikhail and Brookes, Emily and Pombo, Ana and Fisher, Cynthia and Skarnes, William C. and Snoek, Tim and Bezstarosti, Karel and Demmers, Jeroen and Klose, Robert J. and Casanova, Miguel and Tavares, Ligia and Brockdorff, Neil and Merkenschlager, Matthias and Fisher, Amanda G.},
  issn         = {1465-7392},
  language     = {eng},
  number       = {6},
  pages        = {618--624},
  publisher    = {Nature Publishing Group},
  series       = {Nature Cell Biology},
  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},
  url          = {http://dx.doi.org/10.1038/ncb2065},
  volume       = {12},
  year         = {2010},
}