| Budget Amount *help |
¥140,140,000 (Direct Cost: ¥107,800,000、Indirect Cost: ¥32,340,000)
Fiscal Year 2024: ¥28,600,000 (Direct Cost: ¥22,000,000、Indirect Cost: ¥6,600,000)
Fiscal Year 2023: ¥28,600,000 (Direct Cost: ¥22,000,000、Indirect Cost: ¥6,600,000)
Fiscal Year 2022: ¥28,600,000 (Direct Cost: ¥22,000,000、Indirect Cost: ¥6,600,000)
Fiscal Year 2021: ¥27,040,000 (Direct Cost: ¥20,800,000、Indirect Cost: ¥6,240,000)
Fiscal Year 2020: ¥27,300,000 (Direct Cost: ¥21,000,000、Indirect Cost: ¥6,300,000)
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| Outline of Final Research Achievements |
In studying cohesin-related rare disorders, CdLS, CHOPS and HP1β-linked syndromes, we achieved major advances in three areas. Chromatin structure: Patient cells showed less cohesin at enhancers and weaker enhancer-promoter loops, leading to target-gene repression and revealing a feedback loop in which loop loss erodes enhancer histone marks. Transcriptional pathology: Immunodepletion assays proved that cohesin’s ATPase activity is essential after CDK9 activation to release Pol II from pausing, defining an energy-dependent checkpoint in elongation. Informatics & networks: ANKRD11 emerged as a new CdLS gene; deep-learning and graph-based models predict cohesin positioning and map disease-specific loops. iPSC- and mouse-based analyses of AFF4, NKAP and CBX1 mutations reproduced neurodevelopmental phenotypes, pinpointing how each variant disrupts transcriptional networks.
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