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Title: Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts.
Authors: Pandian, Ganesh N
Taniguchi, Junichi
Junetha, Syed
Sato, Shinsuke
Han, Le
Saha, Abhijit
Anandhakumar, Chandran
Bando, Toshikazu  kyouindb  KAKEN_id
Nagase, Hiroki
Vaijayanthi, Thangavel
Taylor, Rhys D
Sugiyama, Hiroshi  kyouindb  KAKEN_id
Author's alias: 杉山, 弘
Keywords: DNA
Chemical tools
Issue Date: 24-Jan-2014
Publisher: Nature Publishing Group
Journal title: Scientific reports
Volume: 4
Thesis number: 3843
Abstract: The influential role of the epigenome in orchestrating genome-wide transcriptional activation instigates the demand for the artificial genetic switches with distinct DNA sequence recognition. Recently, we developed a novel class of epigenetically active small molecules called SAHA-PIPs by conjugating selective DNA binding pyrrole-imidazole polyamides (PIPs) with the histone deacetylase inhibitor SAHA. Screening studies revealed that certain SAHA-PIPs trigger targeted transcriptional activation of pluripotency and germ cell genes in mouse and human fibroblasts, respectively. Through microarray studies and functional analysis, here we demonstrate for the first time the remarkable ability of thirty-two different SAHA-PIPs to trigger the transcriptional activation of exclusive clusters of genes and noncoding RNAs. QRT-PCR validated the microarray data, and some SAHA-PIPs activated therapeutically significant genes like KSR2. Based on the aforementioned results, we propose the potential use of SAHA-PIPs as reagents capable of targeted transcriptional activation.
Description: 人工スイッチを使った遺伝子コントロールに成功 -治療に役立つ可能性も- 京都大学プレスリリース. 2014-01-24.
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
URI: http://hdl.handle.net/2433/180545
DOI(Published Version): 10.1038/srep03843
PubMed ID: 24457603
Related Link: http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2013_1/140124_1.htm
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