| Project/Area Number |
20770100
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional biochemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
KOBAYASHI Taeko Kyoto University, ウイルス研究所, 助教 (40402804)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 細胞内タンパク質分解 / 転写因子の発現振動(オシレーション) / Hes1 / オシレーション / ES細胞分化 / 不均一性 / Hes7 / タンパク質分解 / ユビキチン化 / リプレッサー活性 / DNA結合 / 二量体化 / リジン残基 |
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| Research Abstract |
The basic helix-loop-helix (bHLH) gene Hes is expressed in an oscillatory manner and regulates the differentiation timings at developmental stages. Oscillatory expression of Hes depends on rapid degradation of the gene products, but the precise mechanisms of both how the degradation of Hes protein are regulated and how the timings of cell differentiation are regulated by Hes oscillation remain unclear. First, we found that some lysine residues are essential not only for the instability of Hes7 protein but also for the transcriptional repressor activity. Second, we found that expression of Hes1 oscillates in mouse embryonic stem (ES) cells every 3-5 hours. ES cells expressing low and high levels of Hes1 tended to differentiate into neural and mesodermal cells, respectively. Furthermore, inactivation of Hes1 facilitated neural differentiation more uniformly at earlier time. We revealed that the cyclic expression of Hes1 gene contributes to heterogeneous differentiation of homogenous ES cell populations.
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