TY - JOUR
T1 - Synthetic Chromatin Acylation by an Artificial Catalyst System
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
N1 - Funding Information:
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).
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/6/8
Y1 - 2017/6/8
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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U2 - 10.1016/j.chempr.2017.04.002
DO - 10.1016/j.chempr.2017.04.002
M3 - Article
AN - SCOPUS:85020304533
SN - 2451-9308
VL - 2
SP - 840
EP - 859
JO - Chem
JF - Chem
IS - 6
ER -