Mechanistic link between DNA methylation and H3K9 trimethylation in mammalian cells mediated by two novel SRA proteins- Np95 and Np97
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 |
Research Field |
System genome science
Genome biology
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Research Institution | Institute of Physical and Chemical Research |
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 |
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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Report
(3 results)
Research Products
(4 results)
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[Journal Article] Activation of Endogenous Retroviruses in Dnmt1-/- ESCs Involves Disruption of SETDB1-Mediated Repression by NP95 Binding to Hemimethylated DNA.2016
Author(s)
Sharif J, Endo TA, Nakayama M, Karimi MM, Shimada M, Katsuyama K, Goyal P, Brind'Amour J, Sun MA, Sun Z, Ishikura T, Mizutani-Koseki Y, Ohara O, Shinkai Y, Nakanishi M, Xie H, Lorincz MC, Koseki H.
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Journal Title
Cell Stem Cell
Volume: Epub ahead of print
Issue: 1
Pages: 999-999
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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