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Analysis of nucleolus-mitochondria network regulated by epigenetic factors

Research Project

Project/Area Number 18H02618
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionKumamoto University

Principal Investigator

NAKAO MITSUYOSHI  熊本大学, 発生医学研究所, 教授 (00217663)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsエピゲノム / 核小体 / ミトコンドリア / 遺伝子 / クロマチン / 代謝
Outline of Final Research Achievements

This study focuses on investigating novel epigenomic mechanisms which functionally link between nucleolus and mitochondria. Using specific siRNAs libraries, we found about 15 epigenetic factors that are involved in structure and function of nucleolus and mitochondria, and identified their target genes by RNA-seq and ChIP-seq. NSD2/WHSC1/MMSET methylase maintains growth-promoting gene activities to protect cellular senescence. In addition, we proposed the phenotypic variation in cellular senescence condition in fibroblasts. Further, LSD1/KDM1A and LSD2/KDM1B demethylases, nuclear enzymes that utilize the flavin adenosine dinucleotide as a cofactor, regulated energy metabolism in myocyte and adipocyte differentiation, respectively. Our findings indicate that these epigenetic factors have an essential role in controlling nucleolus and mitochondria metabolism.

Academic Significance and Societal Importance of the Research Achievements

細胞の代謝の恒常性には、エネルギー(ATP)の合成と消費のバランスが重要である。その大半は、細胞質側のミトコンドリアでATPが合成され、核側の核小体によるリボソーム形成とタンパク質合成でATPが消費されている。このバランスを制御する機序については不明な点が多い。核小体とミトコンドリアの連動性に着目し、新規のエピゲノム制御機構を明らかにすることを目指した。核小体-ミトコンドリアのネットワークの基軸解明に迫り、生理と病態への関わりを明らかにするという学術的・社会的な意義がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (62 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (17 results) Journal Article (16 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 16 results,  Open Access: 15 results) Presentation (18 results) (of which Int'l Joint Research: 4 results,  Invited: 16 results) Book (7 results) Remarks (1 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] Leicester大学/Imperial College, London/Cambridge大学(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Cologne大学(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] 国立衛生学研究所NIH/Texas大学(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Khon Kaen大学(タイ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Novartis Pharma AG(スイス)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research]

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Cologne大学(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Leicester大学/Imperial College, London/Cambridge大学(英国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] 国立衛生学研究所NIH/Texas大学(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Khon Kaen大学(タイ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Novartis Pharma AG(スイス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research]

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Leicester大学/Cambridge大学(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] 国立衛生学研究所/Texas大学(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Novartis Pharma AG(スイス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Cologne大学(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Khon Kaen大学(タイ)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] High glucose-ROS conditions enhance the progression in cholangiocarcinoma via upregulation of MAN2A2 and CHD82021

    • Author(s)
      Thonsri U, Wongkham S, Wongkham C, Hino S, Nakao M, Roytrakul S, Koga T, Seubwai W
    • Journal Title

      Cancer Sci.

      Volume: 112 Issue: 1 Pages: 254-264

    • DOI

      10.1111/cas.14719

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The NSD2/WHSC1/MMSET methyltransferase prevents cellular senescence-associated epigenomic remodeling2020

    • Author(s)
      Hiroshi Tanaka, Tomoka Igata, Kan Etoh, Tomoaki Koga, Shin-ichiro Takebayashi, and Mitsuyoshi Nakao.
    • Journal Title

      Aging Cell

      Volume: - Issue: 7 Pages: 1-12

    • DOI

      10.1111/acel.13173

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cellular Senescence Variation by Metabolic and Epigenomic Remodeling.2020

    • Author(s)
      Nakao M, Tanaka H, Koga T.
    • Journal Title

      Trends Cell Biol

      Volume: 30 Issue: 12 Pages: 919-922

    • DOI

      10.1016/j.tcb.2020.08.009

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful generation of epigenetic disease model mice by targeted demethylation of the epigenome.2020

    • Author(s)
      Horii T, Morita S, Hino S, Kimura M, Hino Y, Kogo H, Nakao M & Hatada I
    • Journal Title

      Genome Biology

      Volume: 21(1) Issue: 1 Pages: 77-77

    • DOI

      10.1186/s13059-020-01991-8

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BRD4 promotes metastatic potential in oral squamous cell carcinoma through the epigenetic regulation of the MMP2 gene2020

    • Author(s)
      Yamamoto Tatsuro、Hirosue Akiyuki、Nakamoto Masafumi、Yoshida Ryoji、Sakata Junki、Matsuoka Yuichiro、Kawahara Kenta、Nagao Yuka、Nagata Masashi、Takahashi Nozomu、Hiraki Akimitsu、Shinohara Masanori、Nakao Mitsuyoshi、Saitoh Noriko、Nakayama Hideki
    • Journal Title

      British Journal of Cancer

      Volume: 123 Issue: 4 Pages: 580-590

    • DOI

      10.1038/s41416-020-0907-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Splicing- and demethylase-independent functions of LSD1 in zebrafish primitive hematopoiesis2020

    • Author(s)
      Tamaoki Junya、Takeuchi Miki、Abe Ryo、Kaneko Hiroshi、Wada Taeko、Hino Shinjiro、Nakao Mitsuyoshi、Furukawa Yusuke、Kobayashi Makoto
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 8521-8521

    • DOI

      10.1038/s41598-020-65428-9

    • NAID

      120007163350

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation.2020

    • Author(s)
      Tomoaki Koga, Fumiyuki Sasaki, Kazuko Saeki, Soken Tsuchiya, Toshiaki Okuno, Mai Ohba, Takako Ichiki, Satoshi Iwamoto, Hirotsugu Uzawa, Keiko Kitajima, Chikara Meno, Eri Nakamura, Norihiro Tada, Yoshinori Fukui, Junichi Kikuta, Masaru Ishii, Yukihiko Sugimoto, and Mitsuyoshi Nakao, Takehiko Yokomizo.
    • Journal Title

      Cellular & Molecular Immunology

      Volume: 8 Issue: 6 Pages: 1-13

    • DOI

      10.1038/s41423-020-00559-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Computational analysis of morphological and molecular features in gastric cancer tissues.2020

    • Author(s)
      Yasuda Y, Tokunaga K, Koga T, Goldberg I, Sakamoto C, *Saitoh N, *Nakao M
    • Journal Title

      Cancer Med

      Volume: 9 Issue: 6 Pages: 2223-2234

    • DOI

      10.1002/cam4.2885

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct roles of NAD+-Sirt1 and FAD-LSD1 pathways in metabolic response and tissue development2019

    • Author(s)
      M. Nakao, K. Anan, H. Araki, and S. Hino.
    • Journal Title

      Trends Endocrinol. Metab.

      Volume: 30 Issue: 7 Pages: 409-412

    • DOI

      10.1016/j.tem.2019.04.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysine-specific demethylase-2 is distinctively involved in brown and beige adipogenic differentiation2019

    • Author(s)
      Takase Ryuta、Hino Shinjiro、Nagaoka Katsuya、Anan Kotaro、Kohrogi Kensaku、Araki Hirotaka、Hino Yuko、Sakamoto Akihisa、Nicholson Thomas B.、Chen Taiping、Nakao Mitsuyoshi
    • Journal Title

      The FASEB Journal

      Volume: 33 Issue: 4 Pages: 5300-5311

    • DOI

      10.1096/fj.201801422rr

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis.2019

    • Author(s)
      †Abdalla MOA, †Yamamoto T, Maehara K, Ohkawa Y, Miura H, Hiratani I, Nakayama H, Nakao M, *Saitoh N
    • Journal Title

      Nat Commun

      Volume: 10 Issue: 1 Pages: 3778-3778

    • DOI

      10.1038/s41467-019-11378-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice.2019

    • Author(s)
      Acebedo AR, Suzuki K, Hino S, Alcantara MC, Sato Y, Haga H, Matsumoto KI, Nakao M, Shimamura K, Takeo T, Nakagata N, Miyagawa S, Nishinakamura R, Adelstein RS, Yamada G.
    • Journal Title

      Commun. Biol.

      Volume: eCollection Issue: 1 Pages: 95-95

    • DOI

      10.1038/s42003-019-0336-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endocrine therapy-resistant breast cancer model cells are inhibited by soybean glyceollin I through Eleanor non-coding RNA2018

    • Author(s)
      Yamamoto Tatsuro、Sakamoto Chiyomi、Tachiwana Hiroaki、Kumabe Mitsuru、Matsui Toshiro、Yamashita Tadatoshi、Shinagawa Masatoshi、Ochiai Koji、Saitoh Noriko、Nakao Mitsuyoshi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 15202-15202

    • DOI

      10.1038/s41598-018-33227-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer Navigation Strategy for Endocrine Therapy-Resistant Breast Tumors2018

    • Author(s)
      Nakao Mitsuyoshi、Fujiwara Saori、Iwase Hirotaka
    • Journal Title

      Trends in Cancer

      Volume: 4 Issue: 6 Pages: 404-407

    • DOI

      10.1016/j.trecan.2018.04.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] LSD1 mediates metabolic reprogramming by glucocorticoids during myogenic differentiation2018

    • Author(s)
      K. Anan, S. Hino, N. Shimizu, A. Sakamoto, K. Nagaoka, R. Takase, K. Kohrogi, H. Araki, Y. Hino, S. Usuki, S. Oki, H. Tanaka, K. Nakamura, F. Endo, and M. Nakao
    • Journal Title

      Nucleic Acids Res.

      Volume: 18 Issue: 11 Pages: 5441-5454

    • DOI

      10.1093/nar/gky234

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal undernutrition during early pregnancy inhibits postnatal growth of the tibia in the female offspring of rats by alteration of chondrogenesis2018

    • Author(s)
      Kimura Tomoko、Hino Kodai、Kono Tadaaki、Takano Atsushi、Nitta Norihisa、Ushio Noritoshi、Hino Shinjiro、Takase Ryuta、Kudo Motoi、Daigo Yataro、Morita Wataru、Nakao Mitsuyoshi、Nakatsukasa Masato、Tamagawa Toshihiro、Rafiq Ashiq Mahmood、Matsumoto Akihiro、Otani Hiroki、Udagawa Jun
    • Journal Title

      General and Comparative Endocrinology

      Volume: 260 Issue: 1 Pages: 58-66

    • DOI

      10.1016/j.ygcen.2017.12.008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] エピゲノム制御による表現型バリエーションの分子基盤2021

    • Author(s)
      中尾光善
    • Organizer
      第8回日本骨格筋生物学研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ヒストン脱メチル化酵素KDM7Aによるマクロファージの極性化制御機構2021

    • Author(s)
      古賀友紹、洪性賢、井形朋香、衛藤貫、日野信次朗、中尾光善
    • Organizer
      第14回日本エピジェネティクス研究会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] リボソームタンパク質RPL5 によるリボソームDNA3次元構造と核小体の物性制御2021

    • Author(s)
      松森はるか、渡邉健司、中尾光善、斉藤典子
    • Organizer
      第14回日本エピジェネティクス研究会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 栄養環境に応答するエピゲノム機構と表現型制御2020

    • Author(s)
      中尾光善
    • Organizer
      第34回日本糖尿病・肥満動物学会年次学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] LSD1による環境応答性エピゲノムは骨格筋線維型と代謝型の可塑性に関わる2019

    • Author(s)
      荒木裕貴、日野信次朗、阿南浩太郎、興梠健作、高瀬隆太、中尾光善
    • Organizer
      第42回日本分子生物学会年会(ワークショップ:外部環境要因によるエピゲノム機構の破綻とその制御戦略)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Flavin-dependent histone demethylases link nutrient sensing to metabolic adaptation2019

    • Author(s)
      S. Hino, K. Anan, H. Araki, K. Kohrogi, R. Takase, and M. Nakao
    • Organizer
      第42回日本分子生物学会年会(ワークショップ:Molecular mechanism of various nutrients causing biological reaction)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] エピゲノム機構による表現型制御2019

    • Author(s)
      中尾光善
    • Organizer
      日本人類遺伝学会第64回大会(シンポジウム:エピゲノムの揺らぎと疾患)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] LSD1 inhibition compromises subtype-specific metabolism and sensitizes to iron deprivation in acute myeloid leukemia2019

    • Author(s)
      S. Hino, K. Kohrogi, K. Anan, H. Araki, and M. Nakao
    • Organizer
      Nature Conference on Cellular Metabolism
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 内分泌因子によるエピゲノム制御を介した骨格筋細胞の代謝リプログラミング2018

    • Author(s)
      阿南浩太郎、日野信次朗、高瀬隆太、興梠健作、荒木裕貴、中尾光善
    • Organizer
      第41回日本分子生物学会年会(ワークショップ:ユビキチンonクロマチン)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] エピゲノム因子によるミトコンドリア機能と細胞制御2018

    • Author(s)
      阿南浩太郎、田中宏、井形朋香、荒木裕貴、日野信次朗、中尾光善
    • Organizer
      第41回日本分子生物学会年会(ワークショップ:筋ミトコンドリア研究の新展開)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] エピジェネティクスゲノミクス研究における最近の進歩2018

    • Author(s)
      中尾光善
    • Organizer
      第19回日本分子脳神経外科学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The role of LSD1 family proteins in energy metabolism and pathophysiology2018

    • Author(s)
      M. Nakao
    • Organizer
      International Symposium on Epigenome 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] エピゲノム因子による細胞老化と病態の分子基盤2018

    • Author(s)
      中尾光善
    • Organizer
      第29回フォーラム・イン・ドージン(細胞と個体の老化生物学-科学は不老長寿に迫れるか)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Cancer navigation strategy in endocrine therapy-resistant breast cancer2018

    • Author(s)
      M. Nakao
    • Organizer
      The 34th International Kumamoto Medical Bioscience Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] エピゲノムからDOHaD説を科学する2018

    • Author(s)
      中尾光善
    • Organizer
      第17回生殖バイオロジー東京シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] エネルギー代謝とその病態に関わるエピゲノム記憶2018

    • Author(s)
      中尾光善
    • Organizer
      The 5th Diabetes Research Innovation Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Epigenetic remodeling of energy metabolism and cancer2018

    • Author(s)
      M. Nakao
    • Organizer
      Special Seminar in Khon Kaen University
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] あなたと私はどうして違う? 体質と遺伝子のサイエンス2018

    • Author(s)
      中尾光善
    • Organizer
      日本臨床栄養協会レベルアップセミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] 実験医学増刊(個人差の理解へ向かう肥満症研究)2021

    • Author(s)
      日野信次朗、荒木裕貴、中尾光善
    • Total Pages
      228
    • Publisher
      羊土社
    • Related Report
      2020 Annual Research Report
  • [Book] 糖尿病・内分泌代謝科2020

    • Author(s)
      荒木裕貴、日野信次朗、中尾光善
    • Total Pages
      340
    • Publisher
      科学評論社
    • Related Report
      2020 Annual Research Report
  • [Book] 早産児,低出生体重児の成長と発達のみかた-出生からAYA世代まで-2019

    • Author(s)
      中尾光善
    • Total Pages
      301
    • Publisher
      東京医学社
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Book] 遺伝子医学MOOK別冊(最新遺伝医学研究と遺伝カウンセリング)2019

    • Author(s)
      阿南浩太郎、中尾光善
    • Total Pages
      304
    • Publisher
      メディカル・ドゥ
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Book] 生化学2019

    • Author(s)
      阿南浩太郎、日野信次朗、中尾光善
    • Publisher
      日本生化学会
    • Related Report
      2018 Annual Research Report
  • [Book] 環境とエピゲノム―からだは環境によって変わるのか?―2018

    • Author(s)
      中尾光善
    • Total Pages
      192
    • Publisher
      丸善出版
    • Related Report
      2018 Annual Research Report
  • [Book] 実験医学別冊(がん不均一性を理解し、治療抵抗性に挑む がんはなぜ進化するのか?再発するのか?)2018

    • Author(s)
      藤原沙織、中尾光善
    • Total Pages
      199
    • Publisher
      羊土社
    • Related Report
      2018 Annual Research Report
  • [Remarks] 熊本大学発生医学研究所

    • URL

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

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report
  • [Patent(Industrial Property Rights)] グリセオリンIの作用機序とその利用2019

    • Inventor(s)
      山本達郎;立和田博昭;齋藤典子;中尾光善
    • Industrial Property Rights Holder
      山本達郎;立和田博昭;齋藤典子;中尾光善
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 浮遊性細胞のリアルタイム測定トレイと測定装置、ならびにそれを用いた測定方法2018

    • Inventor(s)
      中尾光善;日野信次朗;興梠健作;岩佐 卓哉;熊谷 聡士
    • Industrial Property Rights Holder
      中尾光善;日野信次朗;興梠健作;岩佐 卓哉;熊谷 聡士
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-178967
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] グリセオリンIの作用機序とその利用2018

    • Inventor(s)
      山本達郎;立齋藤典子;中尾光善;松井利郎;井手剛;落合孝次
    • Industrial Property Rights Holder
      山本達郎;立齋藤典子;中尾光善;松井利郎;井手剛;落合孝次
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-192177
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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