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GENES & DEVELOPMENT 22:1345-1355, 2008
©2008 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-Repressive Complex 2

Diego Pasini, Klaus H. Hansen, Jesper Christensen, Karl Agger, Paul A.C. Cloos, and Kristian Helin1

Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark

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.

[Keywords: EZH2; Polycomb; histone methyl transferase; histone demethylase; epigenetics; embryonic stem cell]

Received January 8, 2008; revised version accepted March 20, 2008.

1 Corresponding author.

E-MAIL kristian.helin{at}bric.dk; FAX 45-3532-5669.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.470008.


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