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Genome mapping of 5-hydroxymethylcytosine using human postmortem brains

Research Project

Project/Area Number 24591676
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionThe University of Tokyo

Principal Investigator

BUNDO Miki  東京大学, 医学部附属病院, 特任助教 (00597221)

Co-Investigator(Renkei-kenkyūsha) IWAMOTO Kazuya  東京大学, 大学院医学系研究科, 特任准教授 (40342753)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsハイドロキシメチルシトシン / DNAメチル化 / ヒト死後脳 / 精神疾患 / 死後脳 / エピジェネティクス / 死後脳研究
Outline of Final Research Achievements

Despite a huge number of studies, the etiology of psychiatric disorders has not been clarified. Recently, 5-hydroxymethylcytosine (5-hmc) was identified as a novel form of modified cytosine, and it is considered as an intermediate form in demethylation step of 5-methylcytosine (5-mc). As the content of 5-hmc in the brain tissues is higher than in any other tissues, it is expected to have the novel roles in the brains.
We have reported that the copy number of Long Interspersed Elements-1 (LINE-1), which has autonomous retrotransposition activity in human genome, increases genomic DNA derived from postmortem brains of patients with major mental disorders, but its mechanism remains unknown. In this study, we have studied the 5-hmc and 5-mc status at LINE-1 regions of genomic DNA from neurons and non-neuronal cells in a healthy human postmortem brain. We found that the content of 5-hmc is especially concentrated at evolutionarily young (active) LINE-1 region in neuronal cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (17 results)

All 2015 2014 2013 2012 Other

All Journal Article (9 results) (of which Peer Reviewed: 7 results,  Open Access: 1 results) Presentation (6 results) (of which Invited: 3 results) Remarks (2 results)

  • [Journal Article] Effects of quetiapine on DNA methylation in neuroblastoma cells.2014

    • Author(s)
      Sugawara H, Bundo M, Asai T, Sunaga F, Ueda J, Ishigooka J, Kasai K, Kato T, Iwamoto K.
    • Journal Title

      Progress in Neuro-Psychopharmacology and Biological Psychiatry

      Volume: 56C Pages: 117-121

    • DOI

      10.1016/j.pnpbp.2014.08.010

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 統合失調症の患者死後脳ではLINE-1配列が増加している2014

    • Author(s)
      文東美紀、加藤忠史、岩本和也
    • Journal Title

      科学

      Volume: 84 Pages: 808-810

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 統合失調症の神経細胞ゲノムではLINE-1のコピー数が増加している2014

    • Author(s)
      文東美紀、加藤忠史、岩本和也
    • Journal Title

      実験医学

      Volume: 32 Pages: 1257-1260

    • Related Report
      2014 Annual Research Report
  • [Journal Article] DNA methylation analysis of BDNF gene promoters in peripheral blood cells of schizophrenia patients.2013

    • Author(s)
      Ikegame T, Bundo M et al. (equal contribution)
    • Journal Title

      Neuroscience Research

      Volume: 77 Issue: 4 Pages: 208-214

    • DOI

      10.1016/j.neures.2013.08.004

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of mood stabilizers on DNA methylation in human neuroblastoma cells.2013

    • Author(s)
      Asai T, Bundo M et al. (equal contribution)
    • Journal Title

      International Journal of Neuropsychopharmacology

      Volume: 16 Issue: 10 Pages: 2285-2294

    • DOI

      10.1017/s1461145713000710

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuronal cell-type specific DNA methylation patterns of the Cacna1c gene.2013

    • Author(s)
      Nishioka M et al.
    • Journal Title

      International Journal of Developmental Neuroscience

      Volume: 31 Pages: 89-95

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comprehensive DNA methylation analysis of peripheral blood cells derived from patients with first-episode schizophrenia.2013

    • Author(s)
      Nishioka M, Bundo M, Koike S, Takizawa R, Kakiuchi C, Araki T, Kasai K, Iwamoto K
    • Journal Title

      J Hum Genet

      Volume: 58(2) Issue: 2 Pages: 91-7

    • DOI

      10.1038/jhg.2012.140

    • NAID

      10031156430

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A systematic evaluation of whole genome amplification of bisulfite-modified DNA.2012

    • Author(s)
      Bundo Miki, Sunaga Fumiko, Ueda Junko, Kasai Kiyoto, Kato Tadafumi, Iwamoto Kazuya.
    • Journal Title

      Clinical Epigenetics

      Volume: 4 Issue: 1 Pages: 22-22

    • DOI

      10.1186/1868-7083-4-22

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] DNA methylation in schizophrenia: progress and challenges of epigenetic studies.2012

    • Author(s)
      Nishioka Masaki, Bundo Miki, Kasai Kiyoto, Iwamoto Kazuya.
    • Journal Title

      Genome Medicine

      Volume: 4 Issue: 12 Pages: 96-96

    • DOI

      10.1186/gm397

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト死後脳神経細胞・非神経細胞ゲノムにおけるLINE-1のハイドロキシメチル化状態の検証2015

    • Author(s)
      澤井大和、西岡将基、文東美紀、上田順子、石井貴男、鵜飼渉、橋本恵理、笠井清登、加藤忠史、岩本和也
    • Organizer
      第10回統合失調症学会
    • Place of Presentation
      都市センターホテル・東京
    • Year and Date
      2015-03-27 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脳ゲノム解析と精神疾患2014

    • Author(s)
      岩本和也、文東美紀、加藤忠史
    • Organizer
      第37回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜・神奈川
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 双極性障害のエピジェネティクス~セロトニントランスポーターにおける候補遺伝子解析2014

    • Author(s)
      岩本和也、文東美紀、池亀天平、菅原裕子、石郷岡純、笠井清登、加藤忠史
    • Organizer
      第36回日本生物学的精神医学会・第57回日本神経化学会大会シンポジウム
    • Place of Presentation
      奈良県文化会館・奈良
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 統合失調症患者死後脳ではLINE-1コピー数が増大している2014

    • Author(s)
      文東美紀、加藤忠史、岩本和也
    • Organizer
      第8回日本エピジェネティクス研究会年会
    • Place of Presentation
      伊藤国際学術研究センター・東京
    • Year and Date
      2014-05-25 – 2014-05-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ヒト死後脳ゲノムDNAにおけるレトロトランスポゾンのコピー数定量2012

    • Author(s)
      文東美紀
    • Organizer
      日本エピジェネティクス研究会第6回年回
    • Place of Presentation
      東京一ツ橋学術総合センター
    • Related Report
      2012 Research-status Report
  • [Presentation] Increasing of LINE-1 copy number in postmortem brains of psychiatric disorder patients2012

    • Author(s)
      Bundo Miki
    • Organizer
      28th CINP Congress
    • Place of Presentation
      Stockholm, Sweden
    • Related Report
      2012 Research-status Report
  • [Remarks] 東京大学大学院医学系研究科・分子精神医学講座

    • URL

      http://www.molpsy.com/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京大学大学院 医学系研究科 分子精神医学講座

    • URL

      http://www.molpsy.com/

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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