Analysis of LINE-1 retrotransposition using poly(I:C) animal model

• Project/Area Number: 15H04891
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kumamoto University
• Principal Investigator: Iwamoto Kazuya 熊本大学, 大学院生命科学研究部(医), 教授 (40342753)
• Co-Investigator(Renkei-kenkyūsha): BUNDO Miki 熊本大学, 大学院生命科学研究部, 准教授 (00597221) ; KATO Tadafumi 理化学研究所, 脳科学総合研究センター, チームリーダー (30214381) ; KASAI Kiyoto 東京大学, 大学院医学系研究科, 教授 (80322056)
• Research Collaborator: MURATA Yui 熊本大学, 大学院生命科学研究部, 博士研究員 (10802077) ; SAWAMURA Rie 熊本大学, 大学院生命科学研究部, 助教 (80509654) ; KIYOTA Emi 熊本大学, 大学院生命科学研究部, 技術補佐員 ; UCHINUNO Emi 熊本大学, 大学院生命科学研究部, 技術補佐員 ; UEDA Junko 理化学研究所, 脳科学総合研究センター, 技術補佐員
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 体細胞変異 / 統合失調症 / トランスポゾン / 精神疾患 / 脳神経疾患 / ゲノム

Outline of Final Research Achievements

Using poly (I:C) mouse model, we analyzed fetal neural progenitor cells. RNA-seq analysis revealed increased expression of immune response and inflammation-related genes and decreased expression of genes related to neurodevelopment. Protein analysis by iTRAQ showed increased expression of factors suppressing viral activity. In addition, analysis of the cytosine modification status for each of the three active LINE-1 subfamilies in mice identified subfamily dependent epigenetic changes. One subfamily showed decreased cytosine methylation and increased hydroxymethylation, suggesting the possibility of selective activation of retrotransposition activity.

Research Products

• [Journal Article] Identification of somatic mutations in monozygotic twins discordant for psychiatric disorders. (2018)
  • Author(s): Nishioka M, Bundo M, Ueda J, Yoshikawa A, Nishimura F, Sasaki T, Kakiuchi C, Kasai K, Kato T, Iwamoto K.
  • Journal Title: NPJ Schizophr. Volume: 4 Issue: 1 Pages: 7-7
  • DOI: 10.1038/s41537-018-0049-5
  • Peer Reviewed / Open Access
• [Journal Article] DNA methylation analyses of the candidate genes identified by a methylome-wide association study revealed common epigenetic alterations in schizophrenia and bipolar disorder. (2018)
  • Author(s): Sugawara H, Murata Y, Ikegame T, Sawamura R, Shimanaga S, Takeoka Y, Saito T, Ikeda M, Yoshikawa A, Nishimura F, Kawamura Y, Kakiuchi C, Sasaki T, Iwata N, Hashimoto M, Kasai K, Kato T, Bundo M, Iwamoto K.
  • Journal Title: Psychiatry Clin Neurosci Volume: in press Issue: 4 Pages: 245-254
  • DOI: 10.1111/pcn.12645
  • Peer Reviewed / Open Access
• [Journal Article] Identification of somatic mutations in postmortem human brains by whole genome sequencing and their implications for psychiatric disorders. (2018)
  • Author(s): Nishioka M, Bundo M, Ueda J, Katsuoka F, Sato Y, Kuroki Y, Ishii T, Ukai W, Murayama S, Hashimoto E, Nagasaki M, Yasuda J, Kasai K, Kato T, Iwamoto K.
  • Journal Title: Psychiatry Clin Neurosci. Volume: 72 Issue: 4 Pages: 280-294
  • DOI: 10.1111/pcn.12632
  • Peer Reviewed / Open Access
• [Journal Article] An epigenome-wide methylation study of healthy individuals with or without depressive symptoms. (2018)
  • Author(s): Shimada M, Otowa T, Miyagawa T, Umekage T, Kawamura Y, Bundo M, Iwamoto K, Ikegame T, Tochigi M, Kasai K, Kaiya H, Tanii H, Okazaki Y, Tokunaga K, Sasaki T. An epigenome-wide methylation study of healthy individuals with or without depressive symptoms.
  • Journal Title: J Hum Genet Volume: 63 Issue: 3 Pages: 319-326
  • DOI: 10.1038/s10038-017-0382-y
  • Peer Reviewed / Open Access
• [Journal Article] DNA methylation profiling in a neuroblastoma cell line exposed to the antipsychotic perospirone (2018)
  • Author(s): Murata Y, Bundo M, Sunaga F, Kasai K, Iwamoto K.
  • Journal Title: Pharmacopsychiatry Volume: in press Issue: 02 Pages: 63-69
  • DOI: 10.1055/s-0044-101467
  • Peer Reviewed / Open Access
• [Journal Article] Mutations of the glycine cleavage system genes possibly affect the negative symptoms of schizophrenia through metabolomic profile changes (2018)
  • Author(s): Yoshikawa Akane, Nishimura Fumichika, Inai Aya, Eriguchi Yosuke, Nishioka Masaki, Takaya Atsuhiko, Tochigi Mamoru, Kawamura Yoshiya, Umekage Tadashi, Kato Kayoko, Sasaki Tsukasa, Ohashi Yoshiaki, Iwamoto Kazuya, Kasai Kiyoto, Kakiuchi Chihiro
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 72 Issue: 3 Pages: 168-179
  • DOI: 10.1111/pcn.12628
  • Peer Reviewed / Open Access
• [Journal Article] Understanding the epigenetic architecture of psychiatric disorders: modifications and beyond (2018)
  • Author(s): Iwamoto K
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 72 Issue: 4 Pages: 194-194
  • DOI: 10.1111/pcn.12646
  • Open Access
• [Journal Article] DNA methylation and hydroxymethylation analyses of the active LINE-1 subfamilies in mice (2017)
  • Author(s): Murata Y, Bundo M, Ueda J, Kubota-Sakashita M, Kasai K, Kato T, Iwamoto K
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 13624-13624
  • DOI: 10.1038/s41598-017-14165-7
• [Journal Article] Polyunsaturated fatty acid deficiency during neurodevelopment in mice models the prodromal state of schizophrenia through epigenetic changes in nuclear receptor genes (2017)
  • Author(s): Maekawa M、Watanabe A、Iwayama Y、Kimura T、Hamazaki K、Balan S、Ohba H、Hisano Y、Nozaki Y、Ohnishi T、Toyoshima M、Shimamoto C、Iwamoto K、Bundo M、Osumi N、Takahashi E、Takashima A、Yoshikawa T
  • Journal Title: Transl Psychiatry. Volume: 7 Issue: 9 Pages: e1229-e1229
  • DOI: 10.1038/tp.2017.182
  • Peer Reviewed / Open Access
• [Journal Article] Epigenome-wide association study of DNA methylation in panic disorder (2017)
  • Author(s): Shimada-Sugimoto, M., T. Otowa, T. Miyagawa, T. Umekage, Y. Kawamura, M. Bundo, K. Iwamoto, M. Tochigi, K. Kasai, H. Kaiya, H. Tanii, Y. Okazaki, K. Tokunaga and T. Sasaki
  • Journal Title: Clinical Epigenetics Volume: 9 Issue: 1 Pages: 6-6
  • DOI: 10.1186/s13148-016-0307-1
  • Peer Reviewed / Open Access
• [Journal Article] Enrichment of deleterious variants of mitochondrial DNA polymerase gene (POLG1) in bipolar disorder (2016)
  • Author(s): Kasahara T, Ishiwata M, Kakiuchi C, Fuke S, Iwata N, Ozaki N, Kunugi H, Minabe Y, Nakamura K, Iwata Y, Fujii K, Kanba S, Ujike H, Kusumi I, Kataoka M, Matoba N, Takata A, Iwamoto K, Yoshikawa T, Kato T
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: - Issue: 8 Pages: 518-529
  • DOI: 10.1111/pcn.12496
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] ヒト前頭様神経細胞における体細胞ゲノム変異の検出 (2018)
  • Author(s): 文東美紀、加藤忠史、岩本和也
  • Organizer: 第123回日本解剖学会
  • Invited
• [Presentation] Increased hmC levels of active LINE-1 promoter in neural precursor cells of poly(I:C) mouse model (2018)
  • Author(s): Murata Y, Bundo M, Kato T, Iwamoto K
  • Organizer: Keystone symposium
  • Int'l Joint Research
• [Presentation] Comprehensive DNA methylation analysis of peripheral blood cells derived from patients with first-episode schizophrenia. (2017)
  • Author(s): Nishioka M, Bundo M, Kasai K, Iwamoto K
  • Organizer: 第62回日本人類遺伝学会
  • Invited
• [Presentation] ヒト脳組織および一卵性双生児における体細胞変異の検出と精神障害 (2017)
  • Author(s): 西岡将基、文東美紀、笠井清登、加藤忠史、岩本和也
  • Organizer: 第39回日本生物学的精神医学会・第47回日本神経精神薬理学会
  • Invited
• [Presentation] Exploration of the pathophysiological role of epigenetic and genomic variations in brains of patients with major psychiatric disorders (2017)
  • Author(s): Iwamoto K
  • Organizer: The 72nd Fujihara Seminar International Symposium
  • Int'l Joint Research / Invited
• [Presentation] 脳ゲノムの動的特性と精神疾患の発症メカニズムの探索 (2017)
  • Author(s): 岩本和也
  • Organizer: 第113回日本精神神経学会学術総会
  • Invited
• [Presentation] LINE-1 copy number analysis of schizophrenic patients (2017)
  • Author(s): Bundo M, Kato T, Iwamoto K
  • Organizer: The 2nd Tore Nilson/Karolinska Institutet conference in Nobel Forum on clinical epigenetics
  • Int'l Joint Research / Invited
• [Presentation] 神経発達期におけるpoly(I:C)母体曝露によるゲノム・エピゲノム状態への影響 (2016)
  • Author(s): 村田唯、文東美紀、大西新、窪田-坂下美恵、池亀天平、石渡みずほ、須原哲也、笠井清登、加藤忠史、岩本和也
  • Organizer: 第38回日本生物学的精神医学会 ・ 第59回日本神経化学会大会
• [Presentation] 統合失調症神経発達障害モデル動物におけるDNAメチル化解析 (2015)
  • Author(s): 村田唯、文東美紀、窪田美恵、池亀天平、上田順子、宮内妙子、井上良夢、石渡みずほ、笠井清登、加藤忠史、岩本和也
  • Organizer: 第45回日本神経精神薬理学会・第37回日本生物学的精神医学会
  • Place of Presentation: タワーホール船堀
  • Year and Date: 2015-09-24
• [Presentation] 脳神経系細胞におけるゲノム・エピゲノム状態の変動と精神疾患 (2015)
  • Author(s): 岩本和也
  • Organizer: 第45回日本神経精神薬理学会・第37回日本生物学的精神医学会
  • Place of Presentation: タワーホール船堀
  • Year and Date: 2015-09-24
  • Invited
• [Presentation] Analysis of DNA methylation of LINE-1 in poly(I:C) mice (2015)
  • Author(s): Murata Y, Bundo M, Kubota M, Ikegame T, Miyauchi T, Inoue R, Ishiwata M, Kasai K, Kato T, Iwamoto K
  • Organizer: 第38回日本神経科学会
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2015-07-28
• [Presentation] Brain genome and epigenome analyses in psychiatric disorders (2015)
  • Author(s): Bundo M, Kato T, Iwamoto K
  • Organizer: 第38回日本神経科学会
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2015-07-28
  • Invited
• [Presentation] DNA methylation analysis of active LINE-1 subfamiles in an animal model of schizophrenia (2015)
  • Author(s): Murata Y, Bundo M, Kubota M, Ikegame T, Miyauchi T, Inoue R, Ishiwata M, Kasai K, Kato T, Iwamoto K
  • Organizer: FASEB Science Research Conference: Mobile DNA in Mammalian Genomes
  • Place of Presentation: West Palm Beach, フロリダ, アメリカ
  • Year and Date: 2015-06-14
  • Int'l Joint Research
• [Presentation] マウスLINE-1のDNAメチル化およびハイドロキシメチル化率測定系の構築 (2015)
  • Author(s): 村田唯、文東美紀、窪田美恵、笠井清登、加藤忠史、岩本和也
  • Organizer: 第9回エピジェネティクス研究会
  • Place of Presentation: 東京一ツ橋学術総合センター
  • Year and Date: 2015-05-25