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

16 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 - Jun 7 2017
Externally publishedYes

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

All Science Journal Classification (ASJC) codes

  • 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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