• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Analysis of chromatin structure in degenerating neurons

Research Project

Project/Area Number 18H02723
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionNiigata University (2021-2022)
Doshisha University (2018-2020)

Principal Investigator

Yamanaka Tomoyuki  新潟大学, 脳研究所, 准教授 (00381575)

Co-Investigator(Kenkyū-buntansha) 貫名 信行  同志社大学, 脳科学研究科, 教授 (10134595)
岩田 淳  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (40401038)
下郡 智美  国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (30391981)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywordsハンチントン病 / トランスクリプトーム / クロマチン / 転写因子 / 神経変性疾患 / クロマチン免疫沈降 / クロマチン構造 / トランスクリプトミクス / 次世代シーケンス解析
Outline of Final Research Achievements

We performed detail analyses of the transcriptional dysregulation focusing on the neurons affected in Huntington's disease. First, we knocked down NF-Y, a transcription factor shown to be affected in Huntington’s disease, in mouse brain, and then collected the knockdown cells by FACS and subjected them to RNA-seq analysis. We found a neuron-specific ER transcriptome affected by NF-Y dysfunction in brain neurons (Yamanaka et al. Sci Rep. 2020). We also collected striatal medium spiny neurons, the most vulnerable neurons in Huntington's disease, by FACS from mouse disease model, and performed RNA-seq analysis. We identified novel transcriptome dysregulated before the neurodegeneration (Miyazaki, Yamanaka et al. J Biol Chem. 2020).

Academic Significance and Societal Importance of the Research Achievements

ハンチントン病のモデル脳等を使った遺伝子発現解析は多数報告されているが、これらが実際に変性神経細胞の中での変化なのか、グリアなど周りの細胞の応答反応をみているのか、その判断は難しい。本研究では、変性過程にある細胞のみをFACSで回収し網羅的に遺伝子発現解析を行うことにより、ハンチントン病で障害される新たなトランスクリプトームを同定することに成功した。一方、ヒストン修飾に大きな差は見られておらず、これ以外のクロマチン構造変化が関わっていると考えられ、現在も解析を進めている。このメカニズムの制御はより広範の遺伝子発現を正常化できると期待されその同定が急がれる。

Report

(5 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (24 results)

All 2023 2022 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (3 results)

  • [Int'l Joint Research] The University of Texas(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] The University of Texas(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] The University of Texas(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Proteomics-Based Approach Identifies Altered ER Domain Properties by ALS-Linked VAPB Mutation2020

    • Author(s)
      Yamanaka Tomoyuki、Nishiyama Risa、Shimogori Tomomi、Nukina Nobuyuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 7610-7610

    • DOI

      10.1038/s41598-020-64517-z

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FACS-array?based cell purification yields a specific transcriptome of striatal medium spiny neurons in a murine Huntington disease model2020

    • Author(s)
      Miyazaki Haruko、Yamanaka Tomoyuki、Oyama Fumitaka、Kino Yoshihiro、Kurosawa Masaru、Yamada-Kurosawa Mizuki、Yamano Risa、Shimogori Tomomi、Hattori Nobutaka、Nukina Nobuyuki
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 29 Pages: 9768-9785

    • DOI

      10.1074/jbc.ra120.012983

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by NF-Y2020

    • Author(s)
      Yamanaka Tomoyuki、Miyazaki Haruko、Tosaki Asako、Maity Sankar N.、Shimogori Tomomi、Hattori Nobutaka、Nukina Nobuyuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 21714-21714

    • DOI

      10.1038/s41598-020-78682-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Proteomic analysis of subcellular compartments containing disseminated alpha-synuclein seeds2020

    • Author(s)
      Kasahara Junya、Imamura Yukio、Hiyama Akiko、Yamanaka Tomoyuki、Miyazaki Haruko、Nukina Nobuyuki
    • Journal Title

      Neuroscience Research

      Volume: 20 Pages: 30494-6

    • DOI

      10.1016/j.neures.2020.11.009

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preserved proteinase K-resistant core after amplification of alpha-synuclein aggregates: Implication to disease-related structural study2020

    • Author(s)
      Yoshinaga Saki、Yamanaka Tomoyuki、Miyazaki Haruko、Okuzumi Ayami、Hiyama Akiko、Murayama Shigeo、Nukina Nobuyuki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 522 Issue: 3 Pages: 655-661

    • DOI

      10.1016/j.bbrc.2019.11.142

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sequence- and seed-structure-dependent polymorphic fibrils of alpha-synuclein2019

    • Author(s)
      Tanaka Goki、Yamanaka Tomoyuki、Furukawa Yoshiaki、Kajimura Naoko、Mitsuoka Kaoru、Nukina Nobuyuki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

      Volume: 19 Issue: 6 Pages: 30065-1

    • DOI

      10.1016/j.bbadis.2019.02.013

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biochemical and morphological classification of disease-associated alpha-synuclein mutants aggregates2019

    • Author(s)
      Tanaka Goki、Yamanaka Tomoyuki、Furukawa Yoshiaki、Kajimura Naoko、Mitsuoka Kaoru、Nukina Nobuyuki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 508 Issue: 3 Pages: 729-734

    • DOI

      10.1016/j.bbrc.2018.11.200

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-coding RNA Neat1 and Abhd11os expressions are dysregulated in medium spiny neurons of Huntington disease model mice2018

    • Author(s)
      Park Hongsun、Miyazaki Haruko、Yamanaka Tomoyuki、Nukina Nobuyuki
    • Journal Title

      Neuroscience Research

      Volume: - Pages: 30551-0

    • DOI

      10.1016/j.neures.2018.10.013

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid dissemination of alpha-synuclein seeds through neural circuits in an in-vivo prion-like seeding experiment2018

    • Author(s)
      Okuzumi Ayami、Kurosawa Masaru、Hatano Taku、Takanashi Masashi、Nojiri Shuuko、Fukuhara Takeshi、Yamanaka Tomoyuki、Miyazaki Haruko、Yoshinaga Saki、Furukawa Yoshiaki、Shimogori Tomomi、Hattori Nobutaka、Nukina Nobuyuki
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 6 Issue: 1 Pages: 96-96

    • DOI

      10.1186/s40478-018-0587-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Analysis of the molecular mechanism underlying a-synuclein propagation using fish disease models.2023

    • Author(s)
      Tomoyuki Yamanaka, Hideaki Matsui
    • Organizer
      第12回 生理研-脳研-ヒト進化研究センター合同シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] αシヌクレインの変異タンパク質ライブラリを用いた凝集制御部位の検索2022

    • Author(s)
      山中智行、檜山晃子、松井秀彰、貫名信行
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] オルガネラ係留タンパク質VAPBのALS変異による小胞体プロテオーム変化2020

    • Author(s)
      山中智行、西山里瑳、下郡智美、貫名信行
    • Organizer
      第93回日本生化学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Identification of ER sheet/tubule-specific proteomes and its alteration by ALS-linked VAPB mutation2019

    • Author(s)
      山中智行、西山里瑳、下郡智美、貫名信行
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ALS関連遺伝子による小胞体病態とプロテオミクス2019

    • Author(s)
      山中智行
    • Organizer
      2019年度同志社大学ハリス理化学研究所研究発表会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 神経の発生と変性を異なるメカニズムで制御する普遍的転写因子2019

    • Author(s)
      山中智行、下郡智美、貫名信行
    • Organizer
      第71回日本細胞生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Immuno-isolation of different ER membrane domains from cultured cells2018

    • Author(s)
      Yamanaka T, Nishiyama R, Nukina N
    • Organizer
      第70回日本細胞生物学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Biochemical characterization of pathological ER domain isolated from cultured cells2018

    • Author(s)
      Yamanaka T, Nukina N
    • Organizer
      Cold Spring Harbor Laboratory Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A transcriptional factor involved in neurogenesis and degeneration2018

    • Author(s)
      Yamanaka T
    • Organizer
      Burke Neurological Institute Special Seminar
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Remarks] 新潟大学脳研究所

    • URL

      https://www.bri.niigata-u.ac.jp/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 同志社大学大学院脳科学研究科

    • URL

      https://brainscience.doshisha.ac.jp/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 同志社大学大学院脳科学研究科認知記憶加齢部門

    • URL

      http://brainscience.doshisha.ac.jp/introduction/pat/ca.html

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi