| Project/Area Number |
24790290
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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 |
General medical chemistry
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| Research Institution | Nagoya City University |
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Principal Investigator |
NISHIYAMA Atsuya 名古屋市立大学, 医学(系)研究科(研究院), 講師 (50378840)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | DNAメチル化 / ユビキチン化 / DNA複製 / 試験管内系 / クロマチン / Trim28 / Dnmt1 / Uhrf1 / PCNA / ヒストン / ユビキチン |
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| Research Abstract |
Faithful propagation of DNA methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells. However, it is unclear how the maintenance of DNA methylation and DNA replication is coordinated. Using Xenopus egg extracts, we successfully reproduce maintenance DNA methylation in vitro. We found that Uhrf1 has an activity to ubiquitylate histone H3. Dnmt1, which converts hemi-methyl DNA to full-methyl DNA, preferentially associates with ubiquitylated histone H3 in vitro through a region previously identified as a replication foci targeting sequence. We also show that ubiquitin ligase activity of Uhrf1 is essential for Dnmt1 recruitment to DNA replication sites and maintaining DNA methylation in mammalian cultured cells. Our finding represent the first evidence of the mechanistic link between DNA methylation and DNA replication through histone H3 ubiquitylation.
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