| 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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| 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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