| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
We showed that Evi1 (Prdm3), an oncogene commonly overexpressed in leukemia, controls Notch activity in olfactory neural stem cells to prevent premature exit from the self-renewal program in vivo. We found that in the absence of Evi1, nucleosomes occupy the RBP-J binding site, RBP-J binding is prevented, and Hes1 activation fails. Once Evi1 binds the Hes1 locus it does not independently activate transcription. Instead, Evi1 action at the Hes1 promoter alters histone methylation status and nucleosome positioning, and thereby creates a chromatin environment with
high potential for RBP-J access. Upon Notch activation this amplifies RBP-J binding and Hes1 induction. Our data define an Evi1-dependent chromatin control system that directs Notch signaling to maintain the neural stem cell self-renewal program.
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