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

Author

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  • Lukas Lercher

    (University of Oxford, Chemistry Research Laboratory
    Present address: EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany)

  • 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)

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.

Suggested Citation

  • Lukas Lercher & Ritu Raj & Nisha A. Patel & Joshua Price & Shabaz Mohammed & Carol V. Robinson & Christopher J. Schofield & Benjamin G. Davis, 2015. "Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8978
    DOI: 10.1038/ncomms8978
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