Drosophila O-GlcNAc transferase (OGT) is encoded by the Polycomb group (PcG) gene, super sex combs (sxc).
O-linked N-acetylglucosamine transferase (OGT) reversibly modifies serine and threonine residues of many intracellular proteins with a single beta-O-linked N-acetylglucosamine residue (O-GlcNAc), and has been implicated in insulin signaling, neurodegenerative disease, cellular stress response, and other important processes in mammals. OGT also glycosylates RNA polymerase II and various transcription factors, which suggests that it might be directly involved in transcriptional regulation. We report here that the Drosophila OGT is encoded by the Polycomb group (PcG) gene, super sex combs (sxc). Furthermore, major sites of O-GlcNAc modification on polytene chromosomes correspond to PcG protein binding sites. Our results thus suggest a direct role for O-linked glycosylation by OGT in PcG-mediated epigenetic gene silencing, which is important in developmental regulation, stem cell maintenance, genomic imprinting, and cancer. In addition, we observe rescue of sxc lethality by a human Ogt cDNA transgene; thus Drosophila may provide an ideal model to study important functional roles of OGT in mammals.
Sinclair
Donald A R
DA
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada V5A 1S6. dsinclai@sfu.ca or honda@sfu.ca
Syrzycka
Monika
M
Macauley
Matthew S
MS
Rastgardani
Tara
T
Komljenovic
Ivana
I
Vocadlo
David J
DJ
Brock
Hugh W
HW
Honda
Barry M
BM
D000818:Animals; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D002874:Chromosome Mapping; D002875:Chromosomes / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics*; D017344:Genes, Insect; D006801:Humans; D009154:Mutation / Q000235:genetics; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D012097:Repressor Proteins / Q000235:genetics*; D019076:Transgenes
D029721:Drosophila Proteins; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase