Pasini, D. et al. Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-repressive complex 2. Genes Dev. 22, 1345-1355

Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark.
Genes & Development (Impact Factor: 10.8). 06/2008; 22(10):1345-55. DOI: 10.1101/gad.470008
Source: PubMed


Polycomb group (PcG) proteins regulate important cellular processes such as embryogenesis, cell proliferation, and stem cell self-renewal through the transcriptional repression of genes determining cell fate decisions. The Polycomb-Repressive Complex 2 (PRC2) is highly conserved during evolution, and its intrinsic histone H3 Lys 27 (K27) trimethylation (me3) activity is essential for PcG-mediated transcriptional repression. Here, we show a functional interplay between the PRC2 complex and the H3K4me3 demethylase Rbp2 (Jarid1a) in mouse embryonic stem (ES) cells. By genome-wide location analysis we found that Rbp2 is associated with a large number of PcG target genes in mouse ES cells. We show that the PRC2 complex recruits Rbp2 to its target genes, and that this interaction is required for PRC2-mediated repressive activity during ES cell differentiation. Taken together, these results demonstrate an elegant mechanism for repression of developmental genes by the coordinated regulation of epigenetic marks involved in repression and activation of transcription.

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Available from: Karl Agger, May 12, 2014
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    Scientific Reports 05/2014; 4:5008. DOI:10.1038/srep05008 · 5.58 Impact Factor
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    • "The H3K4me3 demethylase, Jarid1a, and the H3K27me3 demethylases, Jmjd3 and UTX, counteract the TrxG and PcG complexes, thereby helping to resolve the bivalent domains during ES cell differentiation. Jarid1a is recruited by the PRC2 complex to PcG target genes in ES cells to repress their expression (Pasini et al., 2008). During ES cell differentiation Jarid1a dissociates from the classical PcG target genes, the Hox genes, resulting in an increased H3K4me3 levels and gene activation (Christensen et al., 2007). "
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