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2016 Fiscal Year Final Research Report

Epigenetic regulation of autism-susceptibility gene, NLGN4X.

Research Project

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Project/Area Number 26460483
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionInstitute for Developmental Research, Aichi Human Service Center

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)

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)
Project Period (FY) 2014-04-01 – 2017-03-31
KeywordsNLGN4X / CpG methylation / MeCP2 / miR-23a / exosome / lncRNA / epigenetic / iPSC
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.

Free Research Field

分子生物学

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Published: 2018-03-22  

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