Synthetic Posttranslational Modifications: Chemical Catalyst-Driven Regioselective Histone Acylation of Native Chromatin

Yoshifumi Amamoto, Yuki Aoi, Nozomu Nagashima, Hiroki Suto, Daisuke Yoshidome, Yasuhiro Arimura, Akihisa Osakabe, Daiki Kato, Hitoshi Kurumizaka, Shigehiro A. Kawashima, Kenzo Yamatsugu, Motomu Kanai

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    Posttranslational modifications (PTMs) of histones play an important role in the complex regulatory mechanisms governing gene transcription, and their dysregulation can cause diseases such as cancer. The lack of methods for site-selectively modifying native chromatin, however, limits our understanding of the functional roles of a specific histone PTM, not as a single mark, but in the intertwined PTM network. Here, we report a synthetic catalyst DMAP-SH (DSH), which activates chemically stable thioesters (including acetyl-CoA) under physiological conditions and transfers various acyl groups to the proximate amino groups. Our data suggest that DSH, conjugated with a nucleosome ligand, such as pyrrole-imidazole-polyamide and LANA (latency-associated nuclear antigen)-peptide, promotes both natural (including acetylation, butyrylation, malonylation, and ubiquitination) and non-natural (azido- and phosphoryl labeling) PTMs on histones in recombinant nucleosomes and/or in native chromatin, at lysine residues close to the DSH moiety. To investigate the validity of our method, we used LANA-DSH to promote histone H2B lysine-120 (K120) acylation, the function of which is largely unknown. H2BK120 acetylation and malonylation modulated higher-order chromatin structures by reducing internucleosomal interactions, and this modulation was further enhanced by histone tail acetylation. This approach, therefore, may have versatile applications for dissecting the regulatory mechanisms underlying chromatin function.

    Original languageEnglish
    Pages (from-to)7568-7576
    Number of pages9
    JournalJournal of the American Chemical Society
    Volume139
    Issue number22
    DOIs
    Publication statusPublished - 2017 Jun 7

    Fingerprint

    Acetylation
    Acylation
    Chemical modification
    Post Translational Protein Processing
    Histones
    Chromatin
    Antigens
    Catalysts
    Nucleosomes
    Lysine
    Histone Code
    Transcription
    Polyamides
    Labeling
    Peptides
    Acetyl Coenzyme A
    Pyrroles
    Ubiquitination
    Nylons
    Genes

    ASJC Scopus subject areas

    • Catalysis
    • Chemistry(all)
    • Biochemistry
    • Colloid and Surface Chemistry

    Cite this

    Synthetic Posttranslational Modifications : Chemical Catalyst-Driven Regioselective Histone Acylation of Native Chromatin. / Amamoto, Yoshifumi; Aoi, Yuki; Nagashima, Nozomu; Suto, Hiroki; Yoshidome, Daisuke; Arimura, Yasuhiro; Osakabe, Akihisa; Kato, Daiki; Kurumizaka, Hitoshi; Kawashima, Shigehiro A.; Yamatsugu, Kenzo; Kanai, Motomu.

    In: Journal of the American Chemical Society, Vol. 139, No. 22, 07.06.2017, p. 7568-7576.

    Research output: Contribution to journalArticle

    Amamoto, Y, Aoi, Y, Nagashima, N, Suto, H, Yoshidome, D, Arimura, Y, Osakabe, A, Kato, D, Kurumizaka, H, Kawashima, SA, Yamatsugu, K & Kanai, M 2017, 'Synthetic Posttranslational Modifications: Chemical Catalyst-Driven Regioselective Histone Acylation of Native Chromatin', Journal of the American Chemical Society, vol. 139, no. 22, pp. 7568-7576. https://doi.org/10.1021/jacs.7b02138
    Amamoto, Yoshifumi ; Aoi, Yuki ; Nagashima, Nozomu ; Suto, Hiroki ; Yoshidome, Daisuke ; Arimura, Yasuhiro ; Osakabe, Akihisa ; Kato, Daiki ; Kurumizaka, Hitoshi ; Kawashima, Shigehiro A. ; Yamatsugu, Kenzo ; Kanai, Motomu. / Synthetic Posttranslational Modifications : Chemical Catalyst-Driven Regioselective Histone Acylation of Native Chromatin. In: Journal of the American Chemical Society. 2017 ; Vol. 139, No. 22. pp. 7568-7576.
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    AU - Suto, Hiroki

    AU - Yoshidome, Daisuke

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    AU - Kato, Daiki

    AU - Kurumizaka, Hitoshi

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