Development of programmable small DNA-binding molecules with epigenetic activity for induction of core pluripotency genes |
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Authors: | Pandian Ganesh N Ohtsuki Akimichi Bando Toshikazu Sato Shinsuke Hashiya Kaori Sugiyama Hiroshi |
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Institution: | Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Sakyo, Kyoto 606-8502, Japan. |
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Abstract: | Epigenetic modifications that govern the gene expression are often overlooked with the design of artificial genetic switches. N-Methylpyrrole-N-methylimidazole (PI) hairpin polyamides are programmable small DNA binding molecules that have been studied in the context of gene regulation. Recently, we synthesized a library of compounds by conjugating PI polyamides with SAHA, a chromatin-modifier. Among these novel compounds, PI polyamide-SAHA conjugate 1 was shown to epigenetically activate pluripotency genes in mouse embryonic fibroblasts. Here, we report the synthesis of the derivatives of conjugate 1 and demonstrate that these epigenetically active molecules could be developed to improve the induction of pluripotency factors. |
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