2017 Fiscal Year Final Research Report
Epigenetic regulation of stem cell aging and organismal aging
| Project/Area Number |
15K06835
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Kanazawa University (2017)
Kyushu University (2015-2016) |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
NAKAYAMA Keiichi 九州大学, 生体防御医学研究所, 教授 (80291508)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | Autism |
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| Outline of Final Research Achievements |
We showed that mice heterozygous for Chd8 mutations manifest ASD-like behavioural characteristics including increased anxiety, repetitive behaviour, and altered social behaviour. CHD8 haploinsufficiency did not result in prominent changes in the expression of a few specific genes but instead gave rise to small but global changes in gene expression in the mouse brain, reminiscent of those in the brains of patients with ASD. Gene set enrichment analysis revealed that neurodevelopment was delayed in the mutant mouse embryos. Furthermore, reduced expression of CHD8 was associated with abnormal activation of RE-1 silencing transcription factor (REST), which suppresses the transcription of many neuronal genes. REST activation was also observed in the brains of humans with ASD, and CHD8 was found to interact physically with REST in the mouse brain.
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| Free Research Field |
Molecular biology
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