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- W2148567923 abstract "Considering the essential role of chromatin remodeling in gene regulation, their directed modulation is of increasing importance. To achieve gene activation by epigenetic modification, we synthesized a series of pyrrole–imidazole polyamide conjugates (PIPs) that can bind to predetermined DNA sequences, and attached them with suberoylanilide hydroxamic acid (SAHA), a potent histone deacetylase inhibitor. As histone modification is associated with pluripotency, these new types of conjugates, termed SAHA–PIPs, were screened for their effect on the expression of induced pluripotent stem cell (iPSC) factors. We found certain SAHA–PIPs that could differentially up-regulate the endogenous expression of Oct-3/4, Nanog, Sox2, Klf4 and c-Myc. SAHA and other SAHA–PIPs did not show such induction; this implies a role for PIPs and their sequence specificity in this differential gene activation. Chromatin immunoprecipitation analysis suggested that SAHA–PIP-mediated gene induction proceeds by histone H3 Lys9 and Lys14 acetylation and Lys4 trimethylation, which are epigenetic features associated with transcriptionally active chromatin." @default.
- W2148567923 created "2016-06-24" @default.
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- W2148567923 date "2011-10-28" @default.
- W2148567923 modified "2023-10-11" @default.
- W2148567923 title "Synthetic Small Molecules for Epigenetic Activation of Pluripotency Genes in Mouse Embryonic Fibroblasts" @default.
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- W2148567923 doi "https://doi.org/10.1002/cbic.201100597" @default.
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