title: Combgap contributes to recruitment of Polycomb group proteins in Drosophila.
abstract: Polycomb group (PcG) proteins are responsible for maintaining the silenced transcriptional state of many developmentally regulated genes. PcG proteins are organized into multiprotein complexes that are recruited to DNA via cis-acting elements known as "Polycomb response elements" (PREs). In Drosophila, PREs consist of binding sites for many different DNA-binding proteins, some known and others unknown. Identification of these DNA-binding proteins is crucial to understanding the mechanism of PcG recruitment to PREs. We report here the identification of Combgap (Cg), a sequence-specific DNA-binding protein that is involved in recruitment of PcG proteins. Cg can bind directly to PREs via GTGT motifs and colocalizes with the PcG proteins Pleiohomeotic (Pho) and Polyhomeotic (Ph) at the majority of PREs in the genome. In addition, Cg colocalizes with Ph at a number of targets independent of Pho. Loss of Cg leads to decreased recruitment of Ph at only a subset of sites; some of these sites are binding sites for other Polycomb repressive complex 1 (PRC1) components, others are not. Our data suggest that Cg can recruit Ph in the absence of PRC1 and illustrate the diversity and redundancy of PcG protein recruitment mechanisms.
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Payal
authors.initials: P
authors.lastname: Ray
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Sandip
authors.initials: S
authors.lastname: De
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Apratim
authors.initials: A
authors.lastname: Mitra
authors.affiliation: Proteomics Centre, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands; Department of Cell Biology, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands.
authors.forename: Karel
authors.initials: K
authors.lastname: Bezstarosti
authors.affiliation: Proteomics Centre, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands; Department of Cell Biology, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands.
authors.forename: Jeroen A A
authors.initials: JA
authors.lastname: Demmers
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Karl
authors.initials: K
authors.lastname: Pfeifer
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; jkassis@mail.nih.gov.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Kassis
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D059372:Nucleotide Motifs / Q000235:genetics; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*; D063146:Polycomb-Group Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C066770:Pc protein, Drosophila; D063146:Polycomb-Group Proteins; D014157:Transcription Factors; C416218:cg protein, Drosophila; C072820:ph-d protein, Drosophila; C113295:pho protein, Drosophila; D004247:DNA; D063150:Polycomb Repressive Complex 1
keywords: Combgap; PREs; PcG recruitment; Polycomb; gene expression