title: O-GlcNAcylation prevents aggregation of the Polycomb group repressor polyhomeotic.
abstract: The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. Drosophila embryos lacking Ogt protein arrest development with a remarkably specific Polycomb phenotype, arising from the failure to repress Polycomb target genes. The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the S/T stretch. We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. We propose that O-GlcNAcylation is needed for Ph to form functional, ordered assemblies via its SAM domain.
authors.affiliation: MPI of Biochemistry, Chromatin and Chromosome Biology, Am Klopferspitz 18, 82152 Martinsried, Germany. Electronic address: gambetta@biochem.mpg.de.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Gambetta
authors.affiliation: MPI of Biochemistry, Chromatin and Chromosome Biology, Am Klopferspitz 18, 82152 Martinsried, Germany. Electronic address: muellerj@biochem.mpg.de.
authors.forename: Jürg
authors.initials: J
authors.lastname: Müller
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D055786:Gene Knockout Techniques / Q000379:methods; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012097:Repressor Proteins; C072820:ph-d protein, Drosophila; D063150:Polycomb Repressive Complex 1; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D000117:Acetylglucosamine