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Comprehensive analysis of 3D nuclear gene position involved in malignant transformation of hypoxic cancer

Research Project

Project/Area Number 18KK0233
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 50:Oncology and related fields
Research InstitutionAsahikawa Medical College (2020-2022)
Tokyo Medical and Dental University (2018-2019)

Principal Investigator

Nakayama Koh  旭川医科大学, 医学部, 教授 (10451923)

Co-Investigator(Kenkyū-buntansha) 谷本 幸介  東京医科歯科大学, 難治疾患研究所, 助教 (60611613)
谷水 直樹  東京大学, 医科学研究所, 准教授 (00333386)
與那城 亮  東京医科歯科大学, 難治疾患研究所, 助教 (60453809)
Project Period (FY) 2018-10-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywords低酸素応答 / 遺伝子発現 / クロマチン構造 / HIF / CREB / 核内遺伝子配置 / ヒストンメチル化 / 染色体構造 / 代謝酵素 / 代謝 / がん
Outline of Final Research Achievements

Under hypoxic conditions, our body regulate multiple physiological responses, such as respiration or metabolism, to adapt to such condition. Hypoxic response is an active process which involves induction of multiple genes. In this study, we used comprehensive imaging approach to identify chromatin structure of hypoxia-inducible genes. As a result, we have identified that conformational change of chromatin is actively taking place under hypoxic condition. However, chromatin conformational change led to either increase or decrease of gene expression depending on genes. We will try to address if there is any rule of gene expression based on chromatin conformation under hypoxic condition in our future study.

Academic Significance and Societal Importance of the Research Achievements

低酸素環境に曝されることにより、がんは悪性形質を獲得して、進展する。がんの悪性化には、さまざまな遺伝子の働きが関与する。この遺伝子発現の一翼を担っているのが低酸素応答である。複数の遺伝子の協調的な働きにより低酸素応答は惹起され、この時にはクロマチン構造の変化が活発に起きている。低酸素応答時の遺伝子発現制御機構を、クロマチン構造変化に焦点を当てて理解することにより、複数の遺伝子を同時に調節することも可能となり、がんの悪性化のプロセスを効率的に阻害するアプローチに結びつくことが期待される。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (31 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (5 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (19 results) (of which Int'l Joint Research: 3 results,  Invited: 7 results) Remarks (4 results)

  • [Int'l Joint Research] 国立衛生研究所(NIH)(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] National Institutes of Health(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] National Institutes of Health(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] National Institutes of Health (NIH)(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] National Institutes of Health (NIH)(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Large-scale mapping of positional changes of hypoxia-responsive genes upon activation.2022

    • Author(s)
      Nakayama K. 他5名
    • Journal Title

      Mol. Biol. Cell.

      Volume: 33 Issue: 8

    • DOI

      10.1091/mbc.e21-11-0593

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prolonged hypoxia decreases nuclear pyruvate dehydrogenase complex and regulates the gene expression.2019

    • Author(s)
      Eguchi K. and Nakayama K.*
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 520 Issue: 1 Pages: 128-135

    • DOI

      10.1016/j.bbrc.2019.09.109

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of Gene Expression under Hypoxic Conditions.2019

    • Author(s)
      Nakayama K.* and Kataoka N.*
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 20 Issue: 13 Pages: 3278-3278

    • DOI

      10.3390/ijms20133278

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 低酸素環境で誘導される小胞体ストレス応答のタンパク質分解による制御機構2022

    • Author(s)
      谷内秀輔、中山 恒
    • Organizer
      日本生化学会大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 乳がんの腫瘍形成におけるピルビン酸デヒドロゲナーゼPDH-E1b の機能解明2022

    • Author(s)
      小林之乃、中山 恒
    • Organizer
      日本薬理学会 北部会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Regulatory mechanism of gene expression during early and late phase of hypoxic response2022

    • Author(s)
      中山 恒
    • Organizer
      日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] がんの低酸素応答における早期と長期の遺伝子発現制御機構の解析2022

    • Author(s)
      中山 恒
    • Organizer
      日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Repositioning of hypoxia-responsive genes in the nucleus under prolonged hypoxic conditions2022

    • Author(s)
      中山 恒
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 低酸素環境に応答した核内遺伝子配置変化の解析2021

    • Author(s)
      中山 恒
    • Organizer
      第72回 日本薬理学会北部会
    • Related Report
      2021 Research-status Report
  • [Presentation] クロマチン動態から考える低酸素下の遺伝子発現制御2021

    • Author(s)
      中山 恒
    • Organizer
      がんとハイポキシア研究会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Hypoxia induces positional changes of genes in the nucleus2021

    • Author(s)
      中山 恒
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Novel role of pyruvate dehydrogenase PDH -regulation of histone acetylation and gene expression in breast cancer cells-2021

    • Author(s)
      中山 恒
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Formation of aberrant tumor metabolism under hypoxic condition2021

    • Author(s)
      中山 恒
    • Organizer
      第94回日本細菌学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Transcriptional and post-transcriptional regulation under hypoxic conditions2020

    • Author(s)
      中山 恒
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Nuclear pyruvate dehydrogenase complex is downregulated during prolonged hypoxia and regulates the gene expression.2020

    • Author(s)
      Nakayama K.
    • Organizer
      Keystone Symposia: Hypoxia
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prolonged hypoxic condition downregulates Pyruvate Dehydrogenase PDH-E1βand controls the tumor growth by altering the metabolic status in breast cancer cells.2019

    • Author(s)
      Nakayama K.
    • Organizer
      27th FAOBMB meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Phd-HIFシステム依存的・非依存的に制御される細胞内エネルギー代謝の分子機構2019

    • Author(s)
      中山 恒
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 核に局在するピルビン酸脱水素酵素PDHを介した遺伝子発現制御機構の解析2019

    • Author(s)
      中山 恒
    • Organizer
      第17回 がんとハイポキシア研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 分子シャペロンTCPファミリーによるピルビン酸脱水素酵素PDHの活性制御機構の解析2019

    • Author(s)
      中山 恒
    • Organizer
      第92回 日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ピルビン酸脱水素酵素PDH-E1βは長期的な低酸素環境で減少してがん性代謝を制御する2018

    • Author(s)
      中山 恒
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 長期低酸素環境はピルビン酸脱水素酵素PDH-E1βを減少させ、がん性代謝を制御する2018

    • Author(s)
      中山 恒
    • Organizer
      第16回がんとハイポキシア研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] Pyruvate dehydrogenase PDH-E1β is downregulated under prolonged hypoxic conditions and regulates tumor growth by altering the metabolic status in cancer cells2018

    • Author(s)
      Koh Nakayama
    • Organizer
      Keystone Symposia Hypoxia
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] 旭川医科大学 薬理学講座

    • URL

      https://www.asahikawa-med.ac.jp/dept/mc/pharma/index.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 旭川医科大学薬理学講座HP

    • URL

      https://www.asahikawa-med.ac.jp/dept/mc/pharma/

    • Related Report
      2021 Research-status Report
  • [Remarks] 薬理学講座HP

    • URL

      http://www.asahikawa-med.ac.jp/dept/mc/pharma/

    • Related Report
      2020 Research-status Report
  • [Remarks] 低酸素生物学研究室HP

    • URL

      http://www.tmd.ac.jp/mri/section/advanced/oxy/labo/index.html

    • Related Report
      2019 Research-status Report 2018 Research-status Report

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Published: 2018-10-12   Modified: 2024-01-30  

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