title: Molecular basis of PRC1 targeting to Polycomb response elements by PhoRC.
abstract: Polycomb group (PcG) protein complexes repress transcription by modifying target gene chromatin. In Drosophila, this repression requires association of PcG protein complexes with cis-regulatory Polycomb response elements (PREs), but the interactions permitting formation of these assemblies are poorly understood. We show that the Sfmbt subunit of the DNA-binding Pho-repressive complex (PhoRC) and the Scm subunit of the canonical Polycomb-repressive complex 1 (PRC1) directly bind each other through their SAM domains. The 1.9 Å crystal structure of the Scm-SAM:Sfmbt-SAM complex reveals the recognition mechanism and shows that Sfmbt-SAM lacks the polymerization capacity of the SAM domains of Scm and its PRC1 partner subunit, Ph. Functional analyses in Drosophila demonstrate that Sfmbt-SAM and Scm-SAM are essential for repression and that PhoRC DNA binding is critical to initiate PRC1 association with PREs. Together, this suggests that PRE-tethered Sfmbt-SAM nucleates PRC1 recruitment and that Scm-SAM/Ph-SAM-mediated polymerization then results in the formation of PRC1-compacted chromatin.
authors.affiliation: Laboratory of Chromatin Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
authors.forename: Felice
authors.initials: F
authors.lastname: Frey
authors.affiliation: Laboratory of Chromatin Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Sheahan
authors.affiliation: Laboratory of Chromatin Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
authors.forename: Katja
authors.initials: K
authors.lastname: Finkl
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
authors.forename: Gabriele
authors.initials: G
authors.lastname: Stoehr
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.affiliation: Department of Structural Cell Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Benda
authors.affiliation: Laboratory of Chromatin Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
authors.forename: Jürg
authors.initials: J
authors.lastname: Müller
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D003461:Crystallography; D029721:Drosophila Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D008958:Models, Molecular; D063150:Polycomb Repressive Complex 1 / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D058105:Polymerization; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020218:Response Elements / Q000502:physiology*
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D063146:Polycomb-Group Proteins; C099357:SCM protein, Drosophila; C542497:Sfmbt protein, Drosophila; D063150:Polycomb Repressive Complex 1
keywords: Drosophila; PRC1; PhoRC; Polycomb response element; SAM domain