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Evidence that ubiquitylated H2B corrals hDot1L on the nucleosomal surface to induce H3K79 methylation

Author

Listed:
  • Linjiao Zhou

    (Princeton University)

  • Matthew T. Holt

    (Laboratory of Synthetic Protein Chemistry, The Rockefeller University)

  • Nami Ohashi

    (Princeton University)

  • Aishan Zhao

    (Princeton University)

  • Manuel M. Müller

    (Princeton University)

  • Boyuan Wang

    (Princeton University
    Laboratory of Synthetic Protein Chemistry, The Rockefeller University)

  • Tom W. Muir

    (Princeton University)

Abstract

Ubiquitylation of histone H2B at lysine 120 (H2B-Ub), a post-translational modification first discovered in 1980, plays a critical role in diverse nuclear processes including the regulation of transcription and DNA damage repair. Herein, we use a suite of protein chemistry methods to explore how H2B-Ub stimulates hDot1L-mediated methylation of histone H3 on lysine 79 (H3K79me). By using semisynthetic ‘designer’ chromatin containing H2B-Ub bearing a site-specifically installed photocrosslinker, here we report an interaction between a functional hotspot on ubiquitin and the N-terminus of histone H2A. Our biochemical studies indicate that this interaction is required for stimulation of hDot1L activity and leads to a repositioning of hDot1L on the nucleosomal surface, which likely places the active site of the enzyme proximal to H3K79. Collectively, our data converge on a possible mechanism for hDot1L stimulation in which H2B-Ub physically ‘corrals’ the enzyme into a productive binding orientation.

Suggested Citation

  • Linjiao Zhou & Matthew T. Holt & Nami Ohashi & Aishan Zhao & Manuel M. Müller & Boyuan Wang & Tom W. Muir, 2016. "Evidence that ubiquitylated H2B corrals hDot1L on the nucleosomal surface to induce H3K79 methylation," Nature Communications, Nature, vol. 7(1), pages 1-9, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10589
    DOI: 10.1038/ncomms10589
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