Development of programmable small molecules capable of switching ON the transcriptional machinery of pluripotency genes.
| Project/Area Number |
24710261
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Chemical biology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SUGIYAMA Hiroshi 京都大学, 理学研究科, 教授 (50183843)
BANDO Toshikazu 京都大学, 理学研究科, 准教授 (20345284)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 人工遺伝子スイッチ / 細胞リプログラミング / 小分子 / 合成生物学 / iPS細胞 / 人口遺伝子スイッチ |
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| Research Abstract |
Artificial transcriptional activators with epigenetic activity can retain the capability of their natural equivalents to rewire transcriptional machinery within a cell. During this tenure, we have demonstrated the potential of our novel small molecules for genome engineering termed `SAHA-PIP` containing sequence-specific pyrrole-imidazole polyamides (PIPs) and SAHA, a histone deacetylase inhibitor. We tailored SAHA-PIPs to distinctively activate the pluripotency genes by triggering transcriptionally permissive chromatin in mouse fibroblasts. We have generated PIP conjugates with fluorescent dyes and those targeting different epigenetic enzymes. In human fibroblasts, a SAHA-PIP got characterized as germ cell gene switch and genome-wide gene analysis revealed the capability of thirty-two distinct small molecules to trigger the transcriptional activation of exclusive developmental genes. Our results contribute to the development of novel chemical approach for controlling cell fate.
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Report
(3 results)
Research Products
(40 results)
