| Project/Area Number |
26870847
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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 |
System genome science
Genome biology
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
SHARIF JAFAR 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (00577968)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | NP95 / Hemimethylated DNA / SETDB1 / H3K9me3 / Endogenous retroviruses / IAP / Placenta / Development / hemi-methylated DNA / LTR-derived sequences / NP95/UHRF1 / NP97/UHRF2 / DNA methylation / H3K9 trimethylation / Conditional KO / ES cells / ChIP |
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| Outline of Final Research Achievements |
In the present project, I investigated the role of the mammalian SRA proteins NP95 and NP97 for regulation of H3K9me3, a repressive epigenetic mark, in mammalian cells. I found that protracted binding of NP95 to hemimethylated DNA sites (cytosine methylation in only one strand of the CpG dyad) leads to transient disruption of H3K9me3-dependent transcriptional silencing. I showed that NP95 binding to naturally occurring hemimethylated sites in the placenta gives rise to dramatic activation of a specific class of CpG-rich endogenous retroviruses (LTR containing DNA sequences) via disruption of H3K9me3 mediated silencing. This pathway is inactive in the embryo proper due to the high fidelity of the NP95-DNMT1 mediated maintenance methylation pathway (Sharif et al, Nature, 2007), which prevent accumulation of hemimethylated DNA. I recently reported these observations in a scientific paper (Sharif et al., Cell Stem cell, 2016).
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