Budget Amount *help |
¥22,230,000 (Direct Cost: ¥17,100,000、Indirect Cost: ¥5,130,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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Outline of Final Research Achievements |
The majority of mammalian gene promoters are associated with specialized genomic regions called CpG islands (CGI) that contribute to regulation of gene expression by attracting specific histone modifying enzymes. However, the precise mechanisms by which how CXXC domain-containing proteins, CXXC1 and KDM2B specifically recognize their target CGIs remain poorly understood. Therefore, in this project, we aim to understand the detailed mechanisms to establish epigenetic modifications at specific loci.Here, by using biochemical approach combined with a mice genetic study, we demonstrated CXXC1 and KDM2B specifically recruit associated complex and induce epigenetic modifications. We also revealed Polycomb-proteasome axis could play a critical role in specification of recruitment of CXXC-associated complexes. Therefore, ubiquitin-proteasome system is involves in polycomb-mediated transcriptional regulation and could serve as a gatekeeper for ensuring a proper epigenetic landscape of CGI.
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