Synthetic Chromatin Acylation by an Artificial Catalyst System

Tadashi Ishiguro, Yoshifumi Amamoto, Kana Tanabe, Jiaan Liu, Hidetoshi Kajino, Akiko Fujimura, Yuki Aoi, Akihisa Osakabe, Naoki Horikoshi, Hitoshi Kurumizaka, Kenzo Yamatsugu, Shigehiro A. Kawashima, Motomu Kanai

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12 Citations (Scopus)

Abstract

Histone acetylation is physiologically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) and constitutes a fundamental regulatory element in gene expression. New types of lysine acylation on histones have recently been identified, but it remains unclear how chromatin function is regulated by divergent types of histone acylation and various enzymes. Here, we report on an approach to modulating histone acylation states synthetically without relying on enzymes. We have developed an artificial catalyst system composed of nucleosome-binding catalysts and acyl donors, which preferentially acetylated or malonylated lysines on histone tails and suppressed intra- and inter-nucleosome interactions similarly to HATs. We demonstrate the utility of our approach by identifying a site-selectivity difference between two HDAC isoforms, Sirt1 and Sirt6, and comparing the functions of histone malonylation and acetylation. Our system is applicable to endogenous chromatin without genetic manipulation; thus, it can be used to dissect the complex regulation of chromatin.

Original languageEnglish
Pages (from-to)840-859
Number of pages20
JournalChem
Volume2
Issue number6
DOIs
Publication statusPublished - 2017 Jun 8

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Keywords

  • acetylation
  • acylation
  • catalyst
  • chromatin
  • HAT
  • HDAC
  • histone
  • malonylation
  • post-translational modification

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Biochemistry
  • Environmental Chemistry
  • Materials Chemistry
  • Biochemistry, medical

Cite this

Ishiguro, T., Amamoto, Y., Tanabe, K., Liu, J., Kajino, H., Fujimura, A., Aoi, Y., Osakabe, A., Horikoshi, N., Kurumizaka, H., Yamatsugu, K., Kawashima, S. A., & Kanai, M. (2017). Synthetic Chromatin Acylation by an Artificial Catalyst System. Chem, 2(6), 840-859. https://doi.org/10.1016/j.chempr.2017.04.002