气候变化领域集成服务门户(CCPortal): Live-cell epigenome manipulation by synthetic histone acetylation catalyst system

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DOI	10.1073/pnas.2019554118
	Live-cell epigenome manipulation by synthetic histone acetylation catalyst system
	Fujiwara Y.; Yamanashi Y.; Fujimura A.; Sato Y.; Kujirai T.; Kurumizaka H.; Kimura H.; Yamatsugu K.; Kawashima S.A.; Kanai M.
发表日期	2021
ISSN	00278424
卷号	118 期号:4
英文摘要	Chemical modifications of histones, such as lysine acetylation and ubiquitination, play pivotal roles in epigenetic regulation of gene expression. Methods to alter the epigenome thus hold promise as tools for elucidating epigenetic mechanisms and as therapeutics. However, an entirely chemical method to introduce histone modifications in living cells without genetic manipulation is unprecedented. Here, we developed a chemical catalyst, PEG-LANA-DSSMe 11, that binds with nucleosome’s acidic patch and promotes regioselective, synthetic histone acetylation at H2BK120 in living cells. The size of polyethylene glycol in the catalyst was a critical determinant for its in-cell metabolic stability, binding affinity to histones, and high activity. The synthetic acetylation promoted by 11 without genetic manipulation competed with and suppressed physiological H2B ubiquitination, a mark regulating chromatin functions, such as transcription and DNA damage response. Thus, the chemical catalyst will be a useful tool to manipulate epigenome for unraveling epigenetic mechanisms in living cells. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Acetylation; Catalyst; Epigenome; Histone; Ubiquitination
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180897
作者单位	Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113-0033, Japan; Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, 226-8503, Japan; Institute for Quantitative Biosciences, University of Tokyo, Tokyo, 113-0033, Japan
推荐引用方式 GB/T 7714	Fujiwara Y.,Yamanashi Y.,Fujimura A.,et al. Live-cell epigenome manipulation by synthetic histone acetylation catalyst system[J],2021,118(4).
APA	Fujiwara Y..,Yamanashi Y..,Fujimura A..,Sato Y..,Kujirai T..,...&Kanai M..(2021).Live-cell epigenome manipulation by synthetic histone acetylation catalyst system.Proceedings of the National Academy of Sciences of the United States of America,118(4).
MLA	Fujiwara Y.,et al."Live-cell epigenome manipulation by synthetic histone acetylation catalyst system".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).