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

Lukas Lercher, Ritu Raj, Nisha A. Patel, Joshua Price, Shabaz Mohammed, Carol V. Robinson, Christopher J. Schofield and Benjamin G. Davis ()
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Lukas Lercher: University of Oxford, Chemistry Research Laboratory
Ritu Raj: University of Oxford, Chemistry Research Laboratory
Nisha A. Patel: University of Oxford, Physical and Theoretical Chemistry Laboratory
Joshua Price: University of Oxford, Chemistry Research Laboratory
Shabaz Mohammed: University of Oxford, Chemistry Research Laboratory
Carol V. Robinson: University of Oxford, Physical and Theoretical Chemistry Laboratory
Christopher J. Schofield: University of Oxford, Chemistry Research Laboratory
Benjamin G. Davis: University of Oxford, Chemistry Research Laboratory

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8978

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