Novel epigenetic regulatory sysytem responding to starvation stress

2018 Fiscal Year Annual Research Report

• Project/Area Number: 16K07346
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: 山口 政光 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
• 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

Outline of Annual Research Achievements

RNAシークェンス解析と特異的な抗体を用いたクロマチン免疫沈降法を併用して、ショウジョウバエヒストンメチル化酵素dG9a依存的に飢餓ストレスに応答して発現が変化する遺伝子群を網羅的に同定する。またdG9aがそれらの遺伝子を制御する仕組みを明らかにする。さらに同様の条件下でメタボローム解析を実施することにより、これらの遺伝子発現にリンクして変動する代謝経路を明らかにする。このように生物個体の生死に関わる飢餓ストレスに応答して作動する新しいエピジェネティック制御の仕組みを明らかにすることが本研究の目的である。
飢餓条件下に置いたショウジョウバエ野生型系統とdG9a欠失変異系統を用いたRNA-seq解析とメタボローム解析を完了し、オートファジーに関連する代謝経路と、それらの経路で重要な働きをする遺伝子の発現がdG9a遺伝子の欠失により異常になることを見出した。またdG9a欠失変異系統の脂肪体ではオートファジー活性が著しく低下していることがわかり、dG9a欠失変異系統ではオートファジーによるエネルギーリサイクル活性の低下により、エネルギーが飢餓後早期に枯渇し、生存率が低下するものと解釈できる。またdG9a欠失変異系統では、飢餓後活動量が以上に増加し、エネルギー低下に拍車がかかることも見出した。これはdG9aのようなエピジェネティック制御因子が生物行動も制御するという新しい発見である。これらの発見は、生物個体の生死に関わる飢餓ストレスに応答して作動する新しいエピジェネティック制御の仕組みとして大きな学問的意義がある。またこれらの現象は他のエピジェネティック制御Rpd3、Tip60についても見られることがわかり、最終年度の成果として論文発表を行った。また本研究を発展させて、いくつかの神経変性疾患原因遺伝子もエピジェネティック制御遺伝子と遺伝学的相互作用することもわかった。

Research Products

• [Int'l Joint Research] Pusan National University(韓国)
  • Country Name: KOREA (REP. OF KOREA)
  • Counterpart Institution: Pusan National University
• [Int'l Joint Research] Chiang Mai University(タイ)
  • Country Name: THAILAND
  • Counterpart Institution: Chiang Mai University
• [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 Pages: 150-158
  • DOI: 10.1016/j.yexcr.2019.03.040.
  • Peer Reviewed
• [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 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. (2019)
  • Author(s): Tsuji Wakisaka, K., Tanaka, R., Hirashima, T., Muraoka, Y., Azuma, Y., Yoshida, H., Tokuda, T., Asada, S., Suda, K., Ichiyanagi, K., Ohno, S., Itoh, M. and Yamaguchi, M.
  • Journal Title: Brain Res. Volume: 1708 Pages: 207-219
  • DOI: 10.1016/j.brainres.2018.12.028.
  • Peer Reviewed
• [Journal Article] Role of smallish gene during Drosophila eye development. (2019)
  • Author(s): Tanaka, R., Miyata, S., Yamaguchi, M. and Yoshida, H.
  • Journal Title: Gene Volume: 684 Pages: 10-19
  • DOI: 10.1016/j.gene.2018.10.056
  • Peer Reviewed
• [Journal Article] Genetic screening of 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. and Yamaguchi, M.
  • Journal Title: Exp. Neurol. Volume: 310 Pages: 1-13
  • DOI: 10.1016/j.expneurol.2018.08.009.
  • Peer Reviewed
• [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. and Yoshida, H.
  • Journal Title: Sci. Rep. Volume: 8 Pages: 12910
  • 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. and Yamaguchi, M.
  • Journal Title: Exp. Cell Res. Volume: 371 Pages: 311-321
  • DOI: 10.1016/j.yexcr.2018.08.001
  • Peer Reviewed
• [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. and Yamaguchi, M.
  • Journal Title: Sci. Rep. Volume: 8 Pages: 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 Volume: 1864 Pages: 3038-3049
  • DOI: 10.1016/j.bbadis.2018.06.017.
  • Peer Reviewed
• [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., 2018.
  • Peer Reviewed / Int'l Joint Research
• [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
• [Book] Drosophila Models for Human Diseases (2018)
  • Author(s): Masamitsu Yamaguchi ed.
  • Total Pages: 308
  • Publisher: Springer
  • ISBN: 978-981-13-0528-3