Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-Repressive Complex 2.
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.
Pasini
Diego
D
Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark.
Hansen
Klaus H
KH
Christensen
Jesper
J
Agger
Karl
K
Cloos
Paul A C
PA
Helin
Kristian
K
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism / Q000502:physiology; D006657:Histones / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism / Q000502:physiology*; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D011496:Protein Methyltransferases; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D056485:Retinoblastoma-Binding Protein 2
D004268:DNA-Binding Proteins; D006657:Histones; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C485614:Kdm5b protein, mouse; D056485:Retinoblastoma-Binding Protein 2; D010089:Oxidoreductases, N-Demethylating; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine