文献

J-GLOBAL ID：202002236890262794   整理番号：20A1261525

神経特異的BAFサブユニットACTL6Bの消失は初期応答遺伝子の抑制を軽減し,劣性自閉症を引き起こす【JST・京大機械翻訳】

Loss of the neural-specific BAF subunit ACTL6B relieves repression of early response genes and causes recessive autism

著者 (72件)： Wenderski Wendy (Department of Pathology, Stanford Medical School, Palo Alto, CA 94305) ,  Wenderski Wendy (Department of Genetics, Stanford Medical School, Palo Alto, CA 94305) ,  Wenderski Wendy (Department of Developmental Biology, Stanford Medical School, Palo Alto, CA 94305) ,  Wenderski Wendy (Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305) ,  Wang Lu (Department of Neuroscience, University of California San Diego, La Jolla, CA 92037) ,  Wang Lu (Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92037) ,  Wang Lu (Rady Children’s Institute of Genomic Medicine, University of California San Diego, La Jolla, CA 92037) ,  Krokhotin Andrey (Department of Pathology, Stanford Medical School, Palo Alto, CA 94305) ,  Krokhotin Andrey (Department of Genetics, Stanford Medical School, Palo Alto, CA 94305) ,  Krokhotin Andrey (Department of Developmental Biology, Stanford Medical School, Palo Alto, CA 94305) ,  Krokhotin Andrey (Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305) ,  Walsh Jessica J. (Nancy Pritztker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford Medical School, Palo Alto, CA 94305) ,  Li Hongjie (Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305) ,  Li Hongjie (Department of Biology, Stanford University, Palo Alto, CA 94305) ,  Shoji Hirotaka (Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 470-1192 Toyoake, Aichi, Japan) ,  Ghosh Shereen (Department of Neuroscience, University of California San Diego, La Jolla, CA 92037) ,  Ghosh Shereen (Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92037) ,  Ghosh Shereen (Rady Children’s Institute of Genomic Medicine, University of California San Diego, La Jolla, CA 92037) ,  George Renee D. (Department of Neuroscience, University of California San Diego, La Jolla, CA 92037) ,  George Renee D. (Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92037) ,  George Renee D. (Rady Children’s Institute of Genomic Medicine, University of California San Diego, La Jolla, CA 92037) ,  Miller Erik L. (Department of Pathology, Stanford Medical School, Palo Alto, CA 94305) ,  Miller Erik L. (Department of Genetics, Stanford Medical School, Palo Alto, CA 94305) ,  Miller Erik L. (Department of Developmental Biology, Stanford Medical School, Palo Alto, CA 94305) ,  Miller Erik L. (Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305) ,  Elias Laura (Department of Pathology, Stanford Medical School, Palo Alto, CA 94305) ,  Elias Laura (Department of Genetics, Stanford Medical School, Palo Alto, CA 94305) ,  Elias Laura (Department of Developmental Biology, Stanford Medical School, Palo Alto, CA 94305) ,  Elias Laura (Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305) ,  Gillespie Mark A. (Institute for Systems Biology, Seattle, WA 98109) ,  Son Esther Y. (Department of Pathology, Stanford Medical School, Palo Alto, CA 94305) ,  Son Esther Y. (Department of Genetics, Stanford Medical School, Palo Alto, CA 94305) ,  Son Esther Y. (Department of Developmental Biology, Stanford Medical School, Palo Alto, CA 94305) ,  Son Esther Y. (Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305) ,  Staahl Brett T. (Department of Pathology, Stanford Medical School, Palo Alto, CA 94305) ,  Staahl Brett T. (Department of Genetics, Stanford Medical School, Palo Alto, CA 94305) ,  Staahl Brett T. (Department of Developmental Biology, Stanford Medical School, Palo Alto, CA 94305) ,  Staahl Brett T. (Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305) ,  Baek Seung Tae (Department of Neuroscience, University of California San Diego, La Jolla, CA 92037) ,  Baek Seung Tae (Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92037) ,  Baek Seung Tae (Rady Children’s Institute of Genomic Medicine, University of California San Diego, La Jolla, CA 92037) ,  Stanley Valentina (Department of Neuroscience, University of California San Diego, La Jolla, CA 92037) ,  Stanley Valentina (Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92037) ,  Stanley Valentina (Rady Children’s Institute of Genomic Medicine, University of California San Diego, La Jolla, CA 92037) ,  Moncada Cynthia (Department of Pathology, Stanford Medical School, Palo Alto, CA 94305) ,  Moncada Cynthia (Department of Genetics, Stanford Medical School, Palo Alto, CA 94305) ,  Moncada Cynthia (Department of Developmental Biology, Stanford Medical School, Palo Alto, CA 94305) ,  Moncada Cynthia (Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305) ,  Shipony Zohar (Department of Pathology, Stanford Medical School, Palo Alto, CA 94305) ,  Shipony Zohar (Department of Genetics, Stanford Medical School, Palo Alto, CA 94305) ,  Shipony Zohar (Department of Developmental Biology, Stanford Medical School, Palo Alto, CA 94305) ,  Shipony Zohar (Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305) ,  Linker Sara B. (Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037) ,  Marchetto Maria C. N. (Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037) ,  Gage Fred H. (Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037) ,  Chen Dillon (Department of Neuroscience, University of California San Diego, La Jolla, CA 92037) ,  Chen Dillon (Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92037) ,  Chen Dillon (Rady Children’s Institute of Genomic Medicine, University of California San Diego, La Jolla, CA 92037) ,  Sultan Tipu (Department of Pediatric Neurology, Institute of Child Health, Children Hospital Lahore, 54000 Lahore, Pakistan) ,  Zaki Maha S. (Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, 12311 Cairo, Egypt) ,  Ranish Jeffrey A. (Institute for Systems Biology, Seattle, WA 98109) ,  Miyakawa Tsuyoshi (Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 470-1192 Toyoake, Aichi, Japan) ,  Luo Liqun (Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305) ,  Luo Liqun (Department of Biology, Stanford University, Palo Alto, CA 94305) ,  Malenka Robert C. (Nancy Pritztker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford Medical School, Palo Alto, CA 94305) ,  Crabtree Gerald R. (Department of Pathology, Stanford Medical School, Palo Alto, CA 94305) ,  Crabtree Gerald R. (Department of Genetics, Stanford Medical School, Palo Alto, CA 94305) ,  Crabtree Gerald R. (Department of Developmental Biology, Stanford Medical School, Palo Alto, CA 94305) ,  Crabtree Gerald R. (Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305) ,  Gleeson Joseph G. (Department of Neuroscience, University of California San Diego, La Jolla, CA 92037) ,  Gleeson Joseph G. (Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92037) ,  Gleeson Joseph G. (Rady Children’s Institute of Genomic Medicine, University of California San Diego, La Jolla, CA 92037)
資料名： Proceedings of the National Academy of Sciences of the United States of America  (Proceedings of the National Academy of Sciences of the United States of America)
巻： 117  号： 18  ページ： 10055-10066  発行年： 2020年 
JST資料番号： D0387A  ISSN： 0027-8424  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： アメリカ合衆国 (USA)  言語： 英語 (EN)

抄録/ポイント： ニューロンにおけるシナプス活性は哺乳類行動に関与する遺伝子の急速な活性化をもたらす。BAF複合体のようなATP依存性クロマチン再モデラーはこれらの応答に寄与し,一般的に転写を活性化すると考えられている。しかし,このような「初期活性化」遺伝子サイレントを維持する機構は謎である。メンデルの劣性自閉症を調べる過程で,著者らは,ニューロンBAF(nBAF)サブユニットACTL6B(最初にBAF53bと命名)において機能喪失突然変異を分離する6つの家族を同定した。従って,ACTL6Bは,Simons Recent Autism Cohortにおいて最も有意に突然変異した遺伝子であった。nBAF複合体の少なくとも14個のサブユニットは自閉症で変異しており,それは自閉症スペクトラム障害(ASD)の主な寄与者となる。患者突然変異は,ニューロンにおいてACTL6B蛋白質を不安定化し,ハエ嗅覚系において間違った糸球体に樹状突起を再構成した。ACTL6Bを欠くヒトとマウスは脳梁低形成を示し,神経連結性の促進におけるACTL6Bの保存的役割を示した。2つの遺伝的背景におけるActl6bノックアウトマウスは,社会的および記憶障害,反復行動,および多動性を含むASD関連行動を示した。驚くべきことに,Actl6bの突然変異はAP1転写因子(Fos,Fosl2,FosB,およびJunb)を含む初期応答遺伝子の抑制を軽減し,AP1結合部位でのクロマチン接近性を増加させ,初期応答転写因子活性と関連した後期応答遺伝子の転写変化を増加させた。したがって,ACTL6B損失は,潜在的機構として示されるニューロン特異的クロマチン抑制の障害を伴う劣性ASDの重要な原因である。Copyright 2020 The Author(s). Published by PNAS. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： ニューロン ,  *遺伝子 ,  クロマチン ,  シナプス ,  タンパク質 ,  突然変異 ,  ヒト ,  結合部位 ,  *サブユニット ,  複合体 ,  *劣性 ,  *自閉症 ,  転写因子 ,  ノックアウトマウス ,  AP-1因子

著者キーワード (5件)： 自閉症 ,  マウスモデル ,  劣性 ,  BAF ,  活動依存性

分類 (5件)： 発生と分化  (EJ16020W) ,  細胞生理一般  (EF02010S) ,  先天性疾患・奇形一般  (GD03010V) ,  中枢神経系  (EJ12030F) ,  生物学的機能  (EB03040U)

タイトルに関連する用語 (8件)： 神経 ,  BAF ,  サブユニット ,  初期 ,  応答 ,  遺伝子 ,  劣性 ,  自閉症