title: Cooperativity, specificity, and evolutionary stability of Polycomb targeting in Drosophila.
abstract: Metazoan genomes are partitioned into modular chromosomal domains containing active or repressive chromatin. In flies, Polycomb group (PcG) response elements (PREs) recruit PHO and other DNA-binding factors and act as nucleation sites for the formation of Polycomb repressive domains. The sequence specificity of PREs is not well understood. Here, we use comparative epigenomics and transgenic assays to show that Drosophila domain organization and PRE specification are evolutionarily conserved despite significant cis-element divergence within Polycomb domains, whereas cis-element evolution is strongly correlated with transcription factor binding divergence outside of Polycomb domains. Cooperative interactions of PcG complexes and their recruiting factor PHO stabilize PHO recruitment to low-specificity sequences. Consistently, PHO recruitment to sites within Polycomb domains is stabilized by PRC1. These data suggest that cooperative rather than hierarchical interactions among low-affinity sequences, DNA-binding factors, and the Polycomb machinery are giving rise to specific and strongly conserved 3D structures in Drosophila.
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schuettengruber
authors.affiliation: Department of Computer Science and Applied Mathematics and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Oded Elkayam
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
authors.forename: Tom
authors.initials: T
authors.lastname: Sexton
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Entrevan
authors.affiliation: Department of Computer Science and Applied Mathematics and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Stern
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
authors.forename: Aubin
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Department of Computer Science and Applied Mathematics and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Eitan
authors.initials: E
authors.lastname: Yaffe
authors.affiliation: Montpellier GenomiX IBiSA, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Parrinello
authors.affiliation: Department of Computer Science and Applied Mathematics and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: amos.tanay@weizmann.ac.il.
authors.forename: Amos
authors.initials: A
authors.lastname: Tanay
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France. Electronic address: giacomo.cavalli@igh.cnrs.fr.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cavalli
mesh_terms: D000818:Animals; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D063146:Polycomb-Group Proteins; D014157:Transcription Factors