title: Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation.
abstract: O-GlcNAcylation is a newly discovered histone modification implicated in transcriptional regulation, but no structural information on the physical effect of GlcNAcylation on chromatin exists. Here, we generate synthetic, pure GlcNAcylated histones and nucleosomes and reveal that GlcNAcylation can modulate structure through direct destabilization of H2A/H2B dimers in the nucleosome, thus promoting an 'open' chromatin state. The results suggest that a plausible molecular basis for one role of histone O-GlcNAcylation in epigenetic regulation is to lower the barrier for RNA polymerase passage and hence increase transcription.
authors: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.
authors: Lukas
authors: L
authors: Lercher
authors: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.
authors: Ritu
authors: R
authors: Raj
authors: Department of Chemistry, University of Oxford, Physical and Theoretical Chemistry Laboratory, South Parks Road, Oxford OX1 3QZ, UK.
authors: Nisha A
authors: NA
authors: Patel
authors: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.
authors: Joshua
authors: J
authors: Price
authors: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.
authors: Shabaz
authors: S
authors: Mohammed
authors: Department of Chemistry, University of Oxford, Physical and Theoretical Chemistry Laboratory, South Parks Road, Oxford OX1 3QZ, UK.
authors: Carol V
authors: CV
authors: Robinson
authors: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.
authors: Christopher J
authors: CJ
authors: Schofield
authors: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.
authors: Benjamin G
authors: BG
authors: Davis
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D002853:Chromatography, Liquid; D002942:Circular Dichroism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D019281:Dimerization; D004586:Electrophoresis; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D042421:Histone Code; D006657:Histones / Q000378:metabolism*; D013058:Mass Spectrometry; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013912:Threonine / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D013912:Threonine; D017351:N-Acetylglucosaminyltransferases; D012321:DNA-Directed RNA Polymerases; D000117:Acetylglucosamine