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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.

Original publication

DOI

10.1038/srep03843

Type

Journal article

Journal

Sci Rep

Publication Date

24/01/2014

Volume

4

Keywords

Animals, Biomarkers, DNA, Epigenesis, Genetic, Fibroblasts, Gene Expression Profiling, Gene Silencing, Genome, Human, Histone Deacetylase Inhibitors, Humans, Hydroxamic Acids, Imidazoles, Mice, Nylons, Oligonucleotide Array Sequence Analysis, Promoter Regions, Genetic, Pyrroles, RNA, Messenger, RNA, Untranslated, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Skin, Transcriptional Activation, Vorinostat