title: Interdependence of PRC1 and PRC2 for recruitment to Polycomb Response Elements.
abstract: Polycomb Group (PcG) proteins are epigenetic repressors essential for control of development and cell differentiation. They form multiple complexes of which PRC1 and PRC2 are evolutionary conserved and obligatory for repression. The targeting of PRC1 and PRC2 is poorly understood and was proposed to be hierarchical and involve tri-methylation of histone H3 (H3K27me3) and/or monoubiquitylation of histone H2A (H2AK118ub). Here, we present a strict test of this hypothesis using the Drosophila model. We discover that neither H3K27me3 nor H2AK118ub is required for targeting PRC complexes to Polycomb Response Elements (PREs). We find that PRC1 can bind PREs in the absence of PRC2 but at many PREs PRC2 requires PRC1 to be targeted. We show that one role of H3K27me3 is to allow PcG complexes anchored at PREs to interact with surrounding chromatin. In contrast, the bulk of H2AK118ub is unrelated to PcG repression. These findings radically change our view of how PcG repression is targeted and suggest that PRC1 and PRC2 can communicate independently of histone modifications.
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, 901 87, Sweden.
authors.forename: Tatyana G
authors.initials: TG
authors.lastname: Kahn
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, 901 87, Sweden.
authors.forename: Eshagh
authors.initials: E
authors.lastname: Dorafshan
authors.affiliation: Friedrich-Alexander University of Erlangen-Nürnberg, Department of Biology, Division of Developmental Biology, Erlangen, D-91058, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Schultheis
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, 901 87, Sweden.
authors.forename: Aman
authors.initials: A
authors.lastname: Zare
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, 901 87, Sweden.|Division of CBRN Defense and Security, Swedish Defense Research Agency, FOI, Umeå, 906 21, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Stenberg
authors.affiliation: Friedrich-Alexander University of Erlangen-Nürnberg, Department of Biology, Division of Developmental Biology, Erlangen, D-91058, Germany.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Reim
authors.affiliation: Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pirrotta
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, 901 87, Sweden yuri.schwartz@umu.se.
authors.forename: Yuri B
authors.initials: YB
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D049750:Genome, Insect; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008869:Microtubule-Associated Proteins; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D054875:Ubiquitination
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; C495328:Feo protein, Drosophila; D006657:Histones; D008869:Microtubule-Associated Proteins; D063146:Polycomb-Group Proteins; D011495:Histone-Lysine N-Methyltransferase; C524066:PRC2 protein, Drosophila; D063150:Polycomb Repressive Complex 1; D008239:Lysine