Title |
Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts
|
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Published in |
Scientific Reports, January 2014
|
DOI | 10.1038/srep03843 |
Pubmed ID | |
Authors |
Ganesh N. Pandian, Junichi Taniguchi, Syed Junetha, Shinsuke Sato, Le Han, Abhijit Saha, Chandran AnandhaKumar, Toshikazu Bando, Hiroki Nagase, Thangavel Vaijayanthi, Rhys D. Taylor, Hiroshi Sugiyama |
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. |
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