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

doi:10.1016/j.chempr.2017.04.002

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

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

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 language	English (US)
Pages (from-to)	840-859
Number of pages	20
Journal	Chem
Volume	2
Issue number	6
DOIs	https://doi.org/10.1016/j.chempr.2017.04.002
State	Published - Jun 8 2017

Funding

We thank M. Carey for the plasmids for the Pol II elongation assay. We also thank H. Komatsu and Z. Haiyan for their preliminary contribution at an early stage of this project, D. Kato for purification of nucleosomes, and all members of our laboratory for valuable discussions. This work was supported by JST ERATO grant JPMJER1103 (to M.K.), by a research grant from Kobayashi International Scholarship Foundation (to M.K.), and in part by MEXT KAKENHI grant 25116002 (to H. Kurumizaka).

Keywords

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

ASJC Scopus subject areas

General Chemistry
Biochemistry
Environmental Chemistry
General Chemical Engineering
Biochemistry, medical
Materials Chemistry

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10.1016/j.chempr.2017.04.002

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title = "Synthetic Chromatin Acylation by an Artificial Catalyst System",

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.",

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

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AU - Ishiguro, Tadashi

AU - Amamoto, Yoshifumi

AU - Tanabe, Kana

AU - Liu, Jiaan

AU - Kajino, Hidetoshi

AU - Fujimura, Akiko

AU - Aoi, Yuki

AU - Osakabe, Akihisa

AU - Horikoshi, Naoki

AU - Kurumizaka, Hitoshi

AU - Yamatsugu, Kenzo

AU - Kawashima, Shigehiro A.

AU - Kanai, Motomu

PY - 2017/6/8

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N2 - 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.

AB - 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.

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KW - HDAC

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KW - malonylation

KW - post-translational modification

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Synthetic Chromatin Acylation by an Artificial Catalyst System

Abstract

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Keywords

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