Molecular mechanisms of epigenetic regulation at the mouse imprinted locus
| Project/Area Number |
26840113
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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 |
Genetics/Chromosome dynamics
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ゲノム刷り込み / DNAメチル化 / エピジェネティクス |
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| Outline of Final Research Achievements |
Parent-of-origin-specific DNA methylation (imprinted methylation) plays a central role in controlling imprinted genes expression in mammals, malfunction of which frequently leads to developmental defects and diseases. However, molecular mechanisms by which the methylation status is established and maintained are not fully understood. We previously demonstrated that the H19 imprinting control region (ICR) sequence of the Igf2/H19 locus possesses intrinsic activity to acquire paternal-allele-specific methylation after fertilization in the ectopic genomic loci. In this study, I generated multiple transgenic mouse lines bearing a series of 5’-truncated H19 ICR fragments, and knockout, as well as transgenic mouse lines, in which candidate regulatory sequences were internally deleted from the H19 ICR. Analyses of these animals revealed that one hundred-ish base-pairs of sequences in the H19 ICR are responsible for methylation acquisition on the paternal allele after fertilization.
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Report
(5 results)
Research Products
(19 results)
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[Journal Article] De novo DNA methylation through the 5'-segment of the H19 ICR maintains its imprint during early embryogenesis2015
Author(s)
Matsuzaki, H., Okamura, E., Takahashi, T., Ushiki, A., Nakamura, T., Nakano, T., Hata, K., Fukamizu, A., and Tanimoto, K.
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Journal Title
Development
Volume: 142
Pages: 3833-3844
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] A role for postfertilization, allele-specific DNA methylation activity in maintaining the imprinted H19 ICR methylation2015
Author(s)
Matsuzaki, H., Okamura, E., Ushiki, A., Takahashi, T., Tanimoto, K.
Organizer
Keystone Symposia (DNA methylation)
Place of Presentation
Keystone (アメリカ合衆国)
Year and Date
2015-03-29 – 2015-04-03
Related Report
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