Elucidation of the pathogenesis of autism through transcription elongation impairment

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19295
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Regional Fish Institute, Ltd (R&D Division) (2023); Kyushu University (2022)
• Principal Investigator: Katayama Yuta リージョナルフィッシュ株式会社(研究開発部), 研究開発部, 主任研究員 (70725085)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 自閉症 / ASD / CHD8 / 転写

Outline of Final Research Achievements

CHD8, one of the most frequently mutated genes in autistic patients, was tested for its function in regulating transcription elongation. Transcription elongation responses were examined in mouse neural stem cells lacking CHD8, and transcription elongation activity was reduced with CHD8 loss. Furthermore, a comprehensive search for CHD8-binding proteins revealed that CHD8 proteins bind to transcription elongation activators, suggesting that CHD8 promotes transcription elongation. Since reduced transcription elongation activity is thought to have a particularly strong effect on long genes, and since many autism-related genes are long, it is speculated that impaired transcription elongation is involved in the development of autism caused by genetic mutations in CHD8.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

自閉症は発症頻度が1％以上と高いうえに有効な治療法が確立されていないため、大きな医学的・社会的問題を生じている神経発達障害である。そこで発症原因の解明と治療法の開発が急務となっていることから、社会的にも研究成果に期待が大きい研究領域である。本研究では転写伸長反応の障害が自閉症の発症原因の1つであることを示唆する結果を得た。この発見は自閉症の病態メカニズムの理解を深め、新たに転写伸長反応を標的とする治療戦略の開発に寄与すると期待される。