Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Junichi Taniguchi
PROVIDER: E-GEOD-53319 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Artificial epigenetic switches are of increasing demand owing to the critical role of the dynamic epigenome in orchestrating genome-wide transcriptional activation. Recently, we divulged that certain epigenetically active small molecules called SAHA-PIPs containing the cell permeable pyrrole-imidazole polyamides (PIPs) as DNA recognition module and a histone deacetylases inhibitor SAHA as functional module, is capable of triggering targeted transcriptional activation of pluripotency and germ cell genes in mouse and human fibroblasts, respectively. Through microarray studies and functional analysis, here we demonstrate the first ever example about the remarkable ability of 32 different SAHA-PIPs to trigger transcriptional activation of their own unique set of genes and noncoding RNAs. QRT-PCR studies validated that certain SAHA-PIPs could induce several therapeutically important genes including KSR2 and SEMA6A to suggest its potential use as reagents capable of targeted transcriptional activation and as probe(s) to identify the functional relevance of the uncharacterized genes. Gene induction by a SAHA-PIP and SAHA was measured after treating human dermal fibroblasts at 48 h time-point. Experiment includes a vehicle (DMSO) treatment as a negative control.
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Project description:Artificial epigenetic switches are of increasing demand owing to the critical role of the dynamic epigenome in orchestrating genome-wide transcriptional activation. Recently, we divulged that certain epigenetically active small molecules called SAHA-PIPs containing the cell permeable pyrrole-imidazole polyamides (PIPs) as DNA recognition module and a histone deacetylases inhibitor SAHA as functional module, is capable of triggering targeted transcriptional activation of pluripotency and germ cell genes in mouse and human fibroblasts, respectively. Through microarray studies and functional analysis, here we demonstrate the first ever example about the remarkable ability of 32 different SAHA-PIPs to trigger transcriptional activation of their own unique set of genes and noncoding RNAs. QRT-PCR studies validated that certain SAHA-PIPs could induce several therapeutically important genes including KSR2 and SEMA6A to suggest its potential use as reagents capable of targeted transcriptional activation and as probe(s) to identify the functional relevance of the uncharacterized genes. Gene induction by a SAHA-PIP and SAHA was measured after treating human dermal fibroblasts at 48 h time-point. Experiment includes a vehicle (DMSO) treatment as a negative control.
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Project description:Artificial epigenetic switches are of increasing demand owing to the critical role of the dynamic epigenome in orchestrating genome-wide transcriptional activation. Recently, we divulged that certain epigenetically active small molecules called SAHA-PIPs containing the cell permeable pyrrole-imidazole polyamides (PIPs) as DNA recognition module and a histone deacetylases inhibitor SAHA as functional module, is capable of triggering targeted transcriptional activation of pluripotency and germ cell genes in mouse and human fibroblasts, respectively. Through microarray studies and functional analysis, here we demonstrate the first ever example about the remarkable ability of 32 different SAHA-PIPs to trigger transcriptional activation of their own unique set of genes and noncoding RNAs. QRT-PCR studies validated that certain SAHA-PIPs could induce several therapeutically important genes including KSR2 and SEMA6A to suggest its potential use as reagents capable of targeted transcriptional activation and as probe(s) to identify the functional relevance of the uncharacterized genes. Gene induction by each individual SAHA-PIP was measured after treating human dermal fibroblasts at 48 h time-point. Two libraries of SAHA-PIPs (SAHA-PIP 1-16 and 17-32) were investigated in different experiments and each experiment includes a vehicle (DMSO) treatment as a negative control.
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