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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 ![]() ![]() Xu, Yufang Qian, Xuhong Sugiyama, Hiroshi ![]() ![]() ![]() |
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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