| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
Geminin negatively regulates DNA replication and chromatin remodeling through the direct interaction with Cdt1 and Brahma/Brg1, respectively. We previously demonstrated that Polycomb-group complex 1 and Hoxb4/Hoxa9 regulate the activity of hematopoietic stem cells (HSCs) through the ubiquitin proteasome system-mediated direct regulation of Geminin protein, and that Geminin suppresses the E2F-mediated transcriptional activity through the regulation of chromatin remodeling. Geminin is known as a regulator of DNA replication as well as chromatin remodeling. In this study, shRNA-mediated knockdown of Geminin and visualization of Geminin in Geminin-EYFP knockin mice further supported our hypothesis that Geminin acts as a key regulator for determining cell fate of HSCs, i.e., cellular quiescence, self-renewal and differentiation.
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