| Budget Amount *help |
¥42,900,000 (Direct Cost: ¥33,000,000、Indirect Cost: ¥9,900,000)
Fiscal Year 2020: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2019: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2018: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2017: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2016: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
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| Outline of Final Research Achievements |
In mammals, CpG dinucleotides are recognized by not only DNA methylation mechanisms but also Polycomb group (PcG)-related silencing mechanisms. We hypothesized these two distinct mechanism may functionally interact at CpG dinucleotides and addressed the impacts of DNA methylation maintenance mechanisms mediated by DNMT1 and NP95 on PcG-mediated silencing. Intriguingly, we found target binding and silencing by PcG factors required DNMT1 but not NP95. Instead, NP95 was required for de-repression of PcG targets induced by DNMT1 depletion. Biochemical studies revealed NP95 is involved to mediate ubiquitination of EED, a core component of PcG complexes, and its proteasomal degradation. This study revealed an unexpected link between DNA methylation mechanisms and PcG factors to mediate PcG-mediated silencing, which contributes to maintain spatiotemporally restricted expression of development/differentiation-related genes to facilitate normal development and maintenance of homeostasis.
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