title: Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster.
abstract: N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing. We find that O-GlcNAc is distributed to specific genomic loci both in cells and in vivo. Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. These data suggest that O-GlcNAc acts through multiple mechanisms to regulate gene expression in Drosophila.
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.|Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Ta-Wei
authors.initials: TW
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Mike
authors.initials: M
authors.lastname: Myschyshyn
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Sinclair
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.|Canadian Glycomics Network, Gunning/Lemieux Chemistry Centre, University of Alberta, Alberta, Canada.
authors.forename: Samy
authors.initials: S
authors.lastname: Cecioni
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Beja
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Honda
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Morin
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.|Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.|Canadian Glycomics Network, Gunning/Lemieux Chemistry Centre, University of Alberta, Alberta, Canada.
authors.forename: David J
authors.identifier: 0000-0001-6897-5558
authors.initials: DJ
authors.lastname: Vocadlo
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics*; D049750:Genome, Insect; D063146:Polycomb-Group Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D063146:Polycomb-Group Proteins; D000117:Acetylglucosamine