Novel epigenetic regulatory sysytem responding to starvation stress

• Project/Area Number: 16K07346
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: Yamaguchi Masamitsu 京都工芸繊維大学, 応用生物学系, 教授 (00182460)
• Co-Investigator(Kenkyū-buntansha): 吉田 英樹 京都工芸繊維大学, 応用生物学系, 准教授 (30570600)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ショウジョウバエ / ヒストンメチル化酵素 / dG9a / RNA-seq / メタボローム / 飢餓ストレス / オートファジー / エピジェネティック制御 / エピジェネシス / クロマチン

Outline of Final Research Achievements

By carrying out the RNA-seq analysis and metabolomics study of wild type Drosophila and dG9a mutants, we have found that metabolic pathways and expression levels of genes related to autophagy become abnormal in the dG9a mutants. In addition, in fat body of the dG9a mutants, activity of autophagy is decreased and energy recycling is failed that result in decrease of viability. Furthermore, dG9a mutants show hyperactivity under starvation conditions that further decrease the energy storage. These observations are important to understand the mechanism underlying epigenetic regulation responding to starvation stress.

Academic Significance and Societal Importance of the Research Achievements

2007年にショウジョウバエG9a突然変異系統ホモ接合体が致死にならないと言う予想外の結果が報告されてから、多くの研究者がdG9aの研究から撤退してしまった。これは生存に必須でない遺伝子は生物に取って重要では無いので、dG9aの研究を続けても大きな成果は得られないであろうと言う推測に基づくものであった。しかしながら本研究により、dG9aが飢餓ストレス下でオートファジーの誘導に関与し、また活動量の抑制にも関与することが明らかになった。このようにdG9aが中心的な役割を果たしている、飢餓ストレスに応答する新しいエピジェネティク制御の仕組みが明らかになったことは大きな学術的意義を持つ。

Research Products

• [Int'l Joint Research] Pusan National University(韓国)
• [Int'l Joint Research] Chiang Mai University(タイ)
• [Int'l Joint Research] 釜山大学(韓国)
• [Journal Article] Regulation of animal behavior by epigenetic regulators. (2019)
  • Author(s): Shimaji, K., Tomida, S. and Yamaguchi M.
  • Journal Title: Front. Biosci. Volume: 24 Pages: 1071-1084
  • Peer Reviewed
• [Journal Article] Neuron-specific knockdown of Drosophila HADHB induces a shortened lifespan, deficient locomotive ability, abnormal motor neuron terminal morphology and learning disability. (2019)
  • Author(s): Li J, Suda K, Ueoka I, Tanaka R, Yoshida H, Okada Y, Okamoto Y, Hiramatsu Y, Takashima H, Yamaguchi M.
  • Journal Title: Exp. Cell Res. Volume: 379 Issue: 2 Pages: 150-158
  • DOI: 10.1016/j.yexcr.2019.03.040
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dystrobrevin is required postsynaptically for homeostatic potentiation at the Drosophila NMJ. (2019)
  • Author(s): Jantrapirom, S., Nimlamool, W., Temviriyanukul, P., Ahmadian, S., Locke, C.J., Davis, G.W., Yamaguchi, M.
  • Journal Title: Biochim. Biophys. Acta Volume: 1865 Issue: 6 Pages: 1579-1591
  • DOI: 10.1016/j.bbadis.2019.03.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] hDystrophin is required for normal synaptic gain in the Drosophila olfactory circuit. (2019)
  • Author(s): Jantrapirom, S., Cao, D., Wang, J., Hing, H., Tabone, C.J., Lantz, K., de Belle, J. S., Qiu, Y.T., Smid, H.M., Yamaguchi, M., Noordermeer, J.N., Fradkin, L.G., Potikanond, S.
  • Journal Title: Brain Res. Volume: 1712 Pages: 158-166
  • DOI: 10.1016/j.brainres.2019.01.039
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Novel roles of Drosophila FUS and Aub responsible for piRNA biogenesis in neuronal disorders. (2018)
  • Author(s): Wakisaka KT, Tanaka R, Hirashima T, Muraoka Y, Azuma Y, Yoshida H, Tokuda T, Asada S, Suda K, Ichiyanagi K, Ohno S, Itoh M, Yamaguchi M.
  • Journal Title: Brain Res. Volume: 18 Pages: 30646-30652
  • DOI: 10.1016/j.brainres.2018.12.028
  • Peer Reviewed / Open Access
• [Journal Article] Role of the smallish gene during Drosophila eye development. (2018)
  • Author(s): Tanaka R, Miyata S, Yamaguchi M, Yoshida H.
  • Journal Title: Gene Volume: 684 Pages: 10-19
  • DOI: 10.1016/j.gene.2018.10.056
  • Peer Reviewed / Open Access
• [Journal Article] Genetic screening of the genes interacting with Drosophila FIG4 identified a novel link between CMT-causing gene and long noncoding RNAs. (2018)
  • Author(s): Muraoka Y, Nakamura A, Tanaka R, Suda K, Azuma Y, Kushimura Y, Lo Piccolo L, Yoshida H, Mizuta I, Tokuda T, Mizuno T, Nakagawa M, Yamaguchi M.
  • Journal Title: Exp. Neurol. Volume: 310 Pages: 1-13
  • DOI: 10.1016/j.expneurol.2018.08.009
  • Peer Reviewed / Open Access
• [Journal Article] The ABD on the nascent polypeptide and PH domain are required for the precise Anillin localization in Drosophila syncytial blastoderm. (2018)
  • Author(s): Hirashima T, Tanaka R, Yamaguchi M, Yoshida H.
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 1-9
  • DOI: 10.1038/s41598-018-31106-0
  • Peer Reviewed / Open Access
• [Journal Article] Hippo, Drosophila MST, is a novel modifier of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS. (2018)
  • Author(s): Azuma Y, Tokuda T, Kushimura Y, Yamamoto I, Mizuta I, Mizuno T, Nakagawa M, Ueyama M, Nagai Y, Iwasaki Y, Yoshida M, Pan D, Yoshida H, Yamaguchi M.
  • Journal Title: Exp Cell Res. Volume: 371 Issue: 2 Pages: 311-321
  • DOI: 10.1016/j.yexcr.2018.08.001
  • Peer Reviewed / Open Access
• [Journal Article] NPM-hMLF1 fusion protein suppresses defects of a Drosophila FTLD model expressing the human FUS gene. (2018)
  • Author(s): Yamamoto I, Azuma Y, Kushimura Y, Yoshida H, Mizuta I, Mizuno T, Ueyama M, Nagai Y, Tokuda T, Yamaguchi M.
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 11291-11291
  • DOI: 10.1038/s41598-018-29716-9
  • Peer Reviewed / Open Access
• [Journal Article] Depletion of Ubiquilin induces an augmentation in soluble ubiquitinated Drosophila TDP-43 to drive neurotoxicity in the fly. (2018)
  • Author(s): Jantrapirom, S., Lo Piccolo, L., Yoshida, H. and Yamaguchi, M.
  • Journal Title: Biochim. Biophys. Acta-Molecular Basis of Disease Volume: 1864 Issue: 9 Pages: 3038-3049
  • DOI: 10.1016/j.bbadis.2018.06.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effect of heterochromatin stability on intestinal stem cell aging in Drosophila. (2018)
  • Author(s): Jeon, H. J., Kim, Y. S., Kim, J. G., Heo, K., Pyo, J. H., Yamaguchi, M. and Yoo, M. A.
  • Journal Title: Mech. Ageing Dev. Volume: 173 Pages: 50-60
  • DOI: 10.1016/j.mad.2018.04.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Overexpression of dJmj differentially affects intestinal stem cells and differentiated enterocytes. (2018)
  • Author(s): Suong, D. N. A., Shimaji, K., Pyo, J.-H., Park, J.-S., Yoshida, H., Yoo, M. and Yamaguchi, M.
  • Journal Title: Cellular Signalling Volume: 42 Pages: 194-210
  • DOI: 10.1016/j.cellsig.2017.10.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Novel Drosophila model for psychiatric disorders including autism spectrum disorder by targeting of ATP-binding cassette protein A. (2018)
  • Author(s): Ueoka, I., Kawashima, H., Konishi, A., Aoki, M., Tanaka, R., Yoshida, H., Maeda, T., Ozaki, M. and Yamaguchi, M.
  • Journal Title: Experimental Neurology Volume: 300 Pages: 51-59
  • DOI: 10.1016/j.expneurol.2017.10.027
  • Peer Reviewed
• [Journal Article] Neuron-specific knockdown of Drosophila PDHB induces reduction of lifespan, deficient locomotive ability, abnormal morphology of motor neuron terminals and photoreceptor axon targeting. (2018)
  • Author(s): Dung, V. M., Suong, D. N. A., Okamaoto, Y., Hiramatsu, Y., Thao, D. T. P., Yoshida, H., Takashima, H., and Yamaguchi, M.
  • Journal Title: Experimental Cell Research Volume: 366 Issue: 2 Pages: 92-102
  • DOI: 10.1016/j.yexcr.2018.02.035
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Novel Drosophila model for mitochondrial diseases by targeting of a solute carrier protein SLC25A46. (2018)
  • Author(s): Suda, K., Ueoka, I., Azuma, Y., Muraoka, Y., Yoshida, H. and Yamaguchi, M.
  • Journal Title: Brain Research Volume: 1689 Pages: 30-44
  • DOI: 10.1016/j.brainres.2018.03.028
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic regulation of starvation-induced autophagy in Drosophila by histone methyltransferase G9a. (2017)
  • Author(s): Thuy An, P. N., Shimaji, K., Tanaka, R., Yoshida, H., Kimura, H., Fukusaki, E. and Yamaguchi, M.
  • Journal Title: Scientific Reports Volume: 7 Pages: 7343-7343
  • Peer Reviewed / Open Access
• [Journal Article] Histone methyltransferase G9a is a key regulator of the starvation-induced behaviors in Drosophila melanogaster. (2017)
  • Author(s): Shimaji, K., Tanaka, R., Maeda, T., Ozaki, M., Yoshida, H., Ohkawa, Y., Sato, T., Suyama, M. and Yamaguchi, M.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 14763-14763
  • DOI: 10.1038/s41598-017-15344-2
  • NAID: 120006368029
  • Peer Reviewed / Open Access
• [Journal Article] The Drosophila DOCK family protein Sponge is required for development of the air sac primodium. (2017)
  • Author(s): Kazushige Morishita, Dang Ngoc Anh Suong, Hideki Yoshida and Masamitsu Yamaguchi.
  • Journal Title: Exp. Cell Res. Volume: 17 Issue: 2 Pages: 30165-30169
  • DOI: 10.1016/j.yexcr.2017.03.044
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genome-wide genetic screen identified the link between dG9a and epidermal growth factor receptor signaling pathway in vivo. (2016)
  • Author(s): Kouhei Shimaji, Takahiro Konishi, Hideki Yoshida, Hiroshi Kimura and Masamitsu Yamaguchi
  • Journal Title: Exp. Cell Res Volume: 346 Issue: 1 Pages: 53-64
  • DOI: 10.1016/j.yexcr.2016.06.013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ④Moyu Goto, Narumi Toda, Kouhei Shimaji, Dang Ngoc-Anh Suong, Nicole Vo, Hiroshi Kimura, Hideki Yoshida, Yoshihiro H. Inoue and Masamitsu Yamaguchi. (2016)
  • Author(s): Moyu Goto, Narumi Toda, Kouhei Shimaji, Dang Ngoc-Anh Suong, Nicole Vo, Hiroshi Kimura, Hideki Yoshida, Yoshihiro H. Inoue and Masamitsu Yamaguchi.
  • Journal Title: Spermatogenesis. Volume: 6 Issue: 3 Pages: e1232023-e1232023
  • DOI: 10.1080/21565562.2016.1232023
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Histone Deacetylase Gene Rpd3 Is Required for Starvation Stress Resistance (2016)
  • Author(s): Ei Nakajima, Kouhei Shimaji, Takanari Umegawachi, Saki Tomida, Hideki Yoshida, Nana Yoshimoto, Shingo Izawa, Hiroshi Kimura and Masamitsu Yamaguchi
  • Journal Title: PLoS One Volume: 11 Issue: 12 Pages: e0167554-e0167554
  • DOI: 10.1371/journal.pone.0167554
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Challenging the rare intractable neurological disease such as ALS and CMT by Drosophila models. (2018)
  • Author(s): Yamaguchi M.
  • Organizer: International Joint Conference on Genetics & Medicine 2018
  • Int'l Joint Research / Invited
• [Presentation] Challenging the autism spectrum disorder by Drosophila model targeting of ABCA. (2018)
  • Author(s): Yamaguchi M.
  • Organizer: 日本生化学会・シンポジウム
  • Invited
• [Presentation] Challenging the rare intractable neurological diseases by Drosophila models. (2018)
  • Author(s): Yamaguchi M.
  • Organizer: Symposium in Cell and Developmental Biology Meeting 2018
  • Invited
• [Presentation] Subcellular localization and functional analyses of Drosophila SLC25A46, mitochondrial disease-causing gene. (2018)
  • Author(s): Suda K., Yoshida H., Yamaguchi M.
  • Organizer: Workshop in Cell and Developmental Biology Meeting 2018
• [Presentation] Drosophila Ubiquilin depletion reveals the impact of proteostasis impairment on locomotive and learning abilities. (2018)
  • Author(s): Jantapirom S., Lo Piccolo L., Yoshida H., Yamaguchi M.
  • Organizer: Workshop in Cell and Developmental Biology Meeting 2018
• [Presentation] Regulation of yorkie gene expression through its own non-coding region. (2018)
  • Author(s): Yoshida H., Umegawachi T., Koshida H., Yamada M., Ohkawa Y., Sato T., Suyama M., Krause H.M., Yamaguchi M.
  • Organizer: Workshop in Cell and Developmental Biology Meeting 2018
• [Presentation] How does Drosophila overcome the starvation stress? (2017)
  • Author(s): Yamaguchi, M.
  • Organizer: The 15th Vietnam-Japan Joint Symposium
  • Int'l Joint Research
• [Presentation] The subcellular localization of yorkie mRNA regulates its functional expression. (2017)
  • Author(s): Yoshida,H., Yamaguchi, M. et al.
  • Organizer: EMBO Conference on RNA Localization and Local Translation
  • Int'l Joint Research
• [Presentation] 飢餓ストレスに応答するエピジェネティック制御因子の研究 (2017)
  • Author(s): 冨田早紀、吉田英樹、山口政光 他
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] ALS原因遺伝子FUSのショウジョウバエホモログCabezaと遺伝学的相互作用するエピジェネティック制御因子の同定 (2017)
  • Author(s): 浅田賢志、吉田英樹、山口政光 他
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] ショウジョウバエCMT原因遺伝子dFIG4の新規遺伝学的相互作用因子としての長鎖非コードRNA,CR18854の同定 (2017)
  • Author(s): 村岡夕香、吉田英樹、山口政光 他
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] ショウジョウバエヒストンアセチル化酵素遺伝子Tip60は飢餓耐性獲得に関与する (2016)
  • Author(s): 冨田早紀、嶋路耕平、中島英、吉田英樹、山口政光
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2016-11-30
• [Presentation] ショウジョウバエ精子形成過程でのエピジェネティック制御因子dJmJ/dJarid2の核小体局在を制御する仕組み (2016)
  • Author(s): 後藤萌、戸田成美、吉田英樹、井上喜博、木村宏、山口政光
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2016-11-30
• [Presentation] Metabolic profiling of Drosophila melanogaster metamorphosis. (2016)
  • Author(s): Phan Nguyen Thuy An, Masamitsu Yamaguchi, Shuichi Shimma, Eiichiro Fukusaki.
  • Organizer: Seminar on Asia Insect and Biomedical Research 2016
  • Place of Presentation: Chiang Mai, Thailand
  • Year and Date: 2016-09-07
  • Int'l Joint Research
• [Book] Drosophila Models for Human Diseases (2018)
  • Author(s): Masamitsu Yamaguchi ed.
  • Total Pages: 308
  • Publisher: Springer
  • ISBN: 9789811305283