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Roles of epigenome readers in environmental adaptation

Research Project

Project/Area Number 21K19513
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
Research InstitutionKumamoto University

Principal Investigator

Hino Shinjiro  熊本大学, 発生医学研究所, 准教授 (00448523)

Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords細胞記憶 / エピゲノム / 栄養環境 / 環境ストレス / クロマチン / 環境応答 / epigenome reader / 代謝可塑性 / H3K4メチル化 / 環境記憶 / 代謝体質 / 生活習慣病
Outline of Research at the Start

胎児期や幼少期の成育環境が加齢後の体質や疾患リスクと結びついていると考えられているが、その仕組みはわかっていない。食事や運動などの環境刺激によってDNAやヒストンタンパク質の化学修飾(エピゲノム)が変化し、その環境ストレスが遺伝子レベルで記憶される。本研究では、エピゲノム記憶を生み出す仕組みを解明するために、epigenome readerと呼ばれるタンパク質群に焦点を当て、その分子機能を解析する。細胞が環境ストレスを記憶する仕組みを遺伝子レベルで解明し、生活習慣病の治療・予防に資する成果を目指す。

Outline of Final Research Achievements

Environmental stress factors such as nutrition exert significant influences on our long-term health but the molecular mechanisms remain obscure. In this study, we examined the effects of metabolic stress such as malnutrition, mitochondria damage, and lactic acidosis on gene expression and epigenome formation. We gained insights into how these factors alter gene expression in the long term, and how they affect the cellular features such as growth, survival, and cell fate. Our findings would contribute to the development of health care strategies for the prevention of metabolic disorders and other stress-induced diseases.

Academic Significance and Societal Importance of the Research Achievements

超高齢社会である日本において、継続的な加療を要する慢性代謝疾患の医療効率化は喫緊の課題である。生活環境ストレスの蓄積が慢性疾患の土台であるとすると、ストレス記憶の遮断により持続的な医療効果が期待できる。このような発想は以前から存在するが、科学技術的な障壁により実現に至っていない。本研究の成果は、新たな医療技術の開発だけでなく、栄養素や機能性成分の適切な摂取による健康増進法の開発に貢献するものである。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (31 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (15 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 11 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results) Remarks (6 results)

  • [Int'l Joint Research] コーンケン大学(タイ)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] ケルン大学(ドイツ)

    • Related Report
      2022 Research-status Report
  • [Journal Article] YAP/BRD4‐controlled ROR1 promotes tumor‐initiating cells and hyperproliferation in pancreatic cancer2023

    • Author(s)
      Yamazaki Masaya、Hino Shinjiro、Usuki Shingo、Miyazaki Yoshihiro、Oda Tatsuya、Nakao Mitsuyoshi、Ito Takaaki、Yamagata Kazuya
    • Journal Title

      The EMBO Journal

      Volume: 42 Issue: 14

    • DOI

      10.15252/embj.2022112614

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ミトコンドリアから細胞核への逆行性シグナルによるエンハンサーリモデリング2023

    • Author(s)
      日野裕子、日野信次朗、中尾光善
    • Journal Title

      医学のあゆみ

      Volume: 286 Pages: 171-172

    • Related Report
      2023 Annual Research Report
  • [Journal Article] LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle2023

    • Author(s)
      Araki Hirotaka、Hino Shinjiro、Anan Kotaro、Kuribayashi Kanji、Etoh Kan、Seko Daiki、Takase Ryuta、Kohrogi Kensaku、Hino Yuko、Ono Yusuke、Araki Eiichi、Nakao Mitsuyoshi
    • Journal Title

      eLife

      Volume: 12

    • DOI

      10.7554/elife.84618

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lactic acidosis induces metabolic and phenotypic reprogramming in cholangiocarcinoma cells via the upregulation of thrombospondin‐12023

    • Author(s)
      Thamrongwaranggoon Ubonrat、Kuribayashi Kanji、Araki Hirotaka、Hino Yuko、Koga Tomoaki、Seubwai Wunchana、Wongkham Sopit、Nakao Mitsuyoshi、Hino Shinjiro
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 4 Pages: 1541-1555

    • DOI

      10.1111/cas.15699

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chromatin Immunoprecipitation Sequencing (ChIP-seq) for Detecting Histone Modifications and Modifiers2023

    • Author(s)
      Hino Shinjiro、Sato Tetsuya、Nakao Mitsuyoshi
    • Journal Title

      Methods in Molecular Biology

      Volume: 2577 Pages: 55-64

    • DOI

      10.1007/978-1-0716-2724-2_4

    • ISBN
      9781071627235, 9781071627242
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial stress induces AREG expression and epigenomic remodeling through c-JUN and YAP-mediated enhancer activation2022

    • Author(s)
      Hino Yuko、Nagaoka Katsuya、Oki Shinya、Etoh Kan、Hino Shinjiro、Nakao Mitsuyoshi
    • Journal Title

      Nucleic Acids Research

      Volume: 50 Issue: 17 Pages: 9765-9779

    • DOI

      10.1093/nar/gkac735

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lactic acidosis promotes aggressive features of cholangiocarcinoma cells via upregulating ALDH1A3 expression through EGFR axis2022

    • Author(s)
      Thamrongwaranggoon Ubonrat、Detarya Marutpong、Seubwai Wunchana、Saengboonmee Charupong、Hino Shinjiro、Koga Tomoaki、Nakao Mitsuyoshi、Wongkham Sopit
    • Journal Title

      Life Sciences

      Volume: 302 Pages: 120648-120648

    • DOI

      10.1016/j.lfs.2022.120648

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biosynthesis of S-adenosyl-methionine enhances aging-related defects in Drosophila oogenesis2022

    • Author(s)
      Hayashi Yoshiki、Kashio Soshiro、Murotomi Kazutoshi、Hino Shinjiro、Kang Woojin、Miyado Kenji、Nakao Mitsuyoshi、Miura Masayuki、Kobayashi Satoru、Namihira Masakazu
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 1-9

    • DOI

      10.1038/s41598-022-09424-1

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] リボフラビンとフラボタンパク質による細胞制御2022

    • Author(s)
      日野信次朗
    • Journal Title

      実験医学増刊(栄養・代謝物シグナルと食品機能)

      Volume: 40 Pages: 1161-1167

    • Related Report
      2022 Research-status Report
  • [Journal Article] Advanced oxidation protein products contribute to chronic kidney disease-induced muscle atrophy by inducing oxidative stress via CD36/NADPH oxidase pathway2021

    • Author(s)
      Kato H, Watanabe H, Imafuku T, Arimura N, Fujita I, Noguchi I, Tanaka S, Nakano T, Tokumaru K, Enoki Y, Maeda H, Hino S, Tanaka M, Matsushita K, Fukagawa M, Maruyama T
    • Journal Title

      J Cachexia Sarcopenia Muscle

      Volume: 12 Issue: 6 Pages: 1832-1847

    • DOI

      10.1002/jcsm.12786

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sexual fate of murine external genitalia development: Conserved transcriptional competency for male-biased genes in both sexes2021

    • Author(s)
      Kajioka Daiki、Suzuki Kentaro、Matsushita Shoko、Hino Shinjiro、Sato Tetsuya、Takada Shuji、Isono Kyoichi、Takeo Toru、Kajimoto Mizuki、Nakagata Naomi、Nakao Mitsuyoshi、Suyama Mikita、DeFalco Tony、Miyagawa Shinichi、Yamada Gen
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 23

    • DOI

      10.1073/pnas.2024067118

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lysine Demethylase 5A is Required for MYC Driven Transcription in Multiple Myeloma2021

    • Author(s)
      Ohguchi H、Park Paul M.C.、wang t、Gryder B E.、Ogiya D、kurata k、zhang x、Li D、pei c、Masuda T、Johansson C、Wimalasena V K、Kim Y、Hino S、Usuki S、Kawano Y、Samur M K、Tai Yu-Tzu、Munshi N C.、Matsuoka M、Ohtsuki S、Nakao M、Minami T、Lauberth S、Khan J、Oppermann U、Durbin A D.、Anderson K C.、Hideshima T、Qi J
    • Journal Title

      Blood Cancer Discovery

      Volume: in press Issue: 4 Pages: 370-387

    • DOI

      10.1158/2643-3230.bcd-20-0108

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] LSD1 defines erythroleukemia metabolism by controlling the lineage-specific transcription factors GATA1 and C/EBPα2021

    • Author(s)
      Kohrogi Kensaku、Hino Shinjiro、Sakamoto Akihisa、Anan Kotaro、Takase Ryuta、Araki Hirotaka、Hino Yuko、Araki Kazutaka、Sato Tetsuya、Nakamura Kimitoshi、Nakao Mitsuyoshi
    • Journal Title

      Blood Advances

      Volume: 5 Issue: 9 Pages: 2305-2318

    • DOI

      10.1182/bloodadvances.2020003521

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 栄養環境適応におけるエピジェネティクス制御機構2021

    • Author(s)
      日野信次朗
    • Journal Title

      基礎老化研究

      Volume: 45 Pages: 19-24

    • Related Report
      2021 Research-status Report
  • [Journal Article] 環境応答性エピゲノム形成と肥満の個人差2021

    • Author(s)
      日野信次朗,荒木裕貴,中尾光善
    • Journal Title

      実験医学増刊(個人差の理解へ向かう肥満症研究)

      Volume: 39 Pages: 761-766

    • Related Report
      2021 Research-status Report
  • [Presentation] フラビン依存性エピゲノム形成因子による細胞制御2024

    • Author(s)
      日野信次朗
    • Organizer
      北海道大学遺伝子病制御研究センターセミナー
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] フラビン依存性ヒストン脱メチル化酵素による環境適応の制御2023

    • Author(s)
      日野信次朗
    • Organizer
      第96回日本生化学会大会(シンポジウム:細胞内ケミカルネットワークの解明と創出)
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ヒストン脱メチル化酵素LSD1による骨格筋環境応答の調節2023

    • Author(s)
      日野信次朗
    • Organizer
      日本体力医学会特別大会(シンポジウム:運動応答臓器におけるエピジェネティクス制御の最前線)
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 環境因子とエピジェネティクス因子の相互作用による骨格筋の「質」と「量」の調節2022

    • Author(s)
      日野信次朗
    • Organizer
      日本基礎老化学会第43回シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Epigenetic regulation of energy metabolism in health and diseases2022

    • Author(s)
      Shinjiro Hino
    • Organizer
      Center of Translational Medicine Seminar, Khon Kaen University
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 栄養シグナルによる代謝型可塑性の制御2022

    • Author(s)
      日野信次朗
    • Organizer
      日本栄養・食糧学会関東支部 第108回シンポジウム(栄養シグナルによる生体の代謝制御)
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 栄養シグナルとエピゲノムの連携による代謝表現型の形成2021

    • Author(s)
      日野信次朗、荒木裕貴、栗林寛至、中尾光善
    • Organizer
      第94回日本生化学会大会(シンポジウム:栄養素代謝による細胞制御とその破綻)
    • Related Report
      2021 Research-status Report
  • [Presentation] 白血病細胞の代謝個性を生み出すエピジェネティクス機構 -多層オミクス解析の基礎と応用-2021

    • Author(s)
      日野信次朗
    • Organizer
      WAKO Web受託セミナー -NGSの基礎から最新トピックスまで-
    • Related Report
      2021 Research-status Report
    • Invited
  • [Remarks] 熊本大学発生医学研究所HP

    • URL

      https://www.imeg.kumamoto-u.ac.jp

    • Related Report
      2023 Annual Research Report
  • [Remarks] 熊大通信

    • URL

      https://www.kumamoto-u.ac.jp/daigakujouhou/kouhou/kouhoushi/kumatu/vol-90

    • Related Report
      2023 Annual Research Report
  • [Remarks] 熊本大学発生医学研究所HP

    • URL

      http://www.imeg.kumamoto-u.ac.jp

    • Related Report
      2022 Research-status Report 2021 Research-status Report
  • [Remarks] プレスリリース「筋肉の過剰な環境適応を抑える仕組みを解明」

    • URL

      https://www.kumamoto-u.ac.jp/whatsnew/seimei-sentankenkyu/20230209

    • Related Report
      2022 Research-status Report
  • [Remarks] プレスリリース「ミトコンドリアから細胞核への逆行性シグナリングと標的遺伝子の解明」

    • URL

      https://www.kumamoto-u.ac.jp/whatsnew/seimei-sentankenkyu/20220913

    • Related Report
      2022 Research-status Report
  • [Remarks] プレスリリース「白血病の代謝の個性を生み出す仕組みを解明」

    • URL

      https://www.kumamoto-u.ac.jp/whatsnew/seimei-sentankenkyu/20210507

    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2025-01-30  

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