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Title: A Synthetic DNA-Binding Domain Guides Distinct Chromatin-Modifying Small Molecules to Activate an Identical Gene Network
Authors: Han, Le
Pandian, Ganesh N.
Chandran, Anandhakumar
Sato, Shinsuke
Taniguchi, Junichi
Kashiwazaki, Gengo
Sawatani, Yoshito
Hashiya, Kaori
Bando, Toshikazu  kyouindb  KAKEN_id
Xu, Yufang
Qian, Xuhong
Sugiyama, Hiroshi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-8923-5946 (unconfirmed)
Author's alias: 佐藤, 慎祐
橋谷, かおり
板東, 俊和
杉山, 弘
Keywords: DNA recognition
epigenetics
gene expression
histone modification
synthetic biolog
Issue Date: 20-Jul-2015
Publisher: Wiley-VCH Verlag
Journal title: Angewandte Chemie International Edition
Volume: 54
Issue: 30
Start page: 8700
End page: 8703
Abstract: Synthetic dual‐function ligands targeting specific DNA sequences and histone‐modifying enzymes were applied to achieve regulatory control over multi‐gene networks in living cells. Unlike the broad array of targeting small molecules for histone deacetylases (HDACs), few modulators are known for histone acetyltransferases (HATs), which play a central role in transcriptional control. As a novel chemical approach to induce selective HAT‐regulated genes, we conjugated a DNA‐binding domain (DBD) “I” to N‐(4‐chloro‐3‐trifluoromethyl‐phenyl)‐2‐ethoxy‐benzamide (CTB), an artificial HAT activator. In vitro enzyme activity assays and microarray studies were used to demonstrate that distinct functional small molecules could be transformed to have identical bioactivity when conjugated with a targeting DBD. This proof‐of‐concept synthetic strategy validates the switchable functions of HDACs and HATs in gene regulation and provides a molecular basis for developing versatile bioactive ligands.
Rights: This is the accepted version of the following article: [Angewandte Chemie International Edition, (2015) 54, 30, 8700-8703] , which has been published in final form at https://doi.org/10.1002/anie.201503607. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
The full-text file will be made open to the public on 15 July 2016 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version.
この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/230861
DOI(Published Version): 10.1002/anie.201503607
PubMed ID: 26094767
Appears in Collections:Journal Articles

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