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  2. Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation

Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation

  • Nat Commun. 2015 Aug 25;6:7978. doi: 10.1038/ncomms8978.
Lukas Lercher 1 Ritu Raj 1 Nisha A Patel 2 Joshua Price 1 Shabaz Mohammed 1 Carol V Robinson 2 Christopher J Schofield 1 Benjamin G Davis 1
Affiliations

Affiliations

  • 1 Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.
  • 2 Department of Chemistry, University of Oxford, Physical and Theoretical Chemistry Laboratory, South Parks Road, Oxford OX1 3QZ, UK.
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.

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