title: Combinatorial interactions are required for the efficient recruitment of pho repressive complex (PhoRC) to polycomb response elements.
abstract: Polycomb Group (PcG) proteins are epigenetic repressors that control metazoan development and cell differentiation. In Drosophila, PcG proteins form five distinct complexes targeted to genes by Polycomb Response Elements (PREs). Of all PcG complexes PhoRC is the only one that contains a sequence-specific DNA binding subunit (PHO or PHOL), which led to a model that places PhoRC at the base of the recruitment hierarchy. Here we demonstrate that in vivo PHO is preferred to PHOL as a subunit of PhoRC and that PHO and PHOL associate with PREs and a subset of transcriptionally active promoters. Although the binding to the promoter sites depends on the quality of recognition sequences, the binding to PREs does not. Instead, the efficient recruitment of PhoRC to PREs requires the SFMBT subunit and crosstalk with Polycomb Repressive Complex 1. We find that human YY1 protein, the ortholog of PHO, binds sites at active promoters in the human genome but does not bind most PcG target genes, presumably because the interactions involved in the targeting to Drosophila PREs are lost in the mammalian lineage. We conclude that the recruitment of PhoRC to PREs is based on combinatorial interactions and propose that such a recruitment strategy is important to attenuate the binding of PcG proteins when the target genes are transcriptionally active. Our findings allow the appropriate placement of PhoRC in the PcG recruitment hierarchy and provide a rationale to explain why YY1 is unlikely to serve as a general recruiter of mammalian Polycomb complexes despite its reported ability to participate in PcG repression in flies.
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Tatyana G
authors.initials: TG
authors.lastname: Kahn
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden; Computational Life Science Cluster (CLiC), Umeå University, Umeå, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Stenberg
authors.affiliation: Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pirrotta
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Yuri B
authors.initials: YB
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004331:Drosophila melanogaster; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D063146:Polycomb-Group Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020218:Response Elements / Q000235:genetics*; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D063146:Polycomb-Group Proteins; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D063150:Polycomb Repressive Complex 1