| Project/Area Number |
26460483
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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 |
Experimental pathology
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
Iio Akio 愛知県心身障害者コロニー発達障害研究所, 発生障害学部, リサーチレジデント (80344349)
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| Co-Investigator(Renkei-kenkyūsha) |
NAKAYAMA Atsuo 愛知県心身障害者コロニー発達障害研究所, 発生障害学部, 部長 (50227964)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | NLGN4X / CpG methylation / MeCP2 / miR-23a / exosome / lncRNA / epigenetic / iPSC / 自閉症 / メチル化 / microRNA / AVP / TOP1 / エピジェネティックス / CpGメチル化 / mTOR / Topoisomerase I |
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| Outline of Final Research Achievements |
Some types of genetic mutation in NLGN4X, including point mutations and copy number variants, are considered responsible for rare autism spectrum disorders. However, it is unclear about the transcriptional and post-transcriptional regulation of NLGN4X expression. Thus, we focus on elucidating how the NLGN4X expression is epigenetically regulated in the neural cell. Firstly, we showed that NLGN4X promoters were silenced by CpG methylation in association with MeCP2. Next, we clarified that NLGN4X was down-regulated by exosomal miR-23a, which secreted by heat-stressed microglia. Finally, we identified a novel natural antisense transcript (AS-NLGN4X), which was partially complementary to NLGN4X exon 1s. Its expression pattern was similar with NLGN4X. Interestingly, forced expression of AS-NLGN4X down-regulated NLGN4X expression, and AS-NLGN4X knockdown up-regulated it. These results suggest that NLGN4X is transcriptionally and/or post-transcriptionally under control by non-coding RNAs.
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