Genome wide screening of genomic DNA demethylation factors by genetic method.

• Project/Area Number: 23616002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: epigenetics
• Research Institution: Hiroshima University
• Principal Investigator: KIKUCHI Yutaka 広島大学, 理学(系)研究科(研究院), 教授 (20286438)
• Co-Investigator(Kenkyū-buntansha): HOZUMI Shunya 広島大学, 大学院理学研究科, 助教 (10597222)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ゼブラフィッシュ / 変異体 / スクリーニング / 脱メチル化 / 発生 / 再生 / 脱メチル化因子

Outline of Final Research Achievements

Epigenetics is a regulatory system for gene expression independent of genomic DNA sequence. Genomic DNA methylation is one of epigenetics system, but the mechanisms of DNA demethylation remain to be elucidated in animal cells. To uncover the DNA demethylation systems in animal cells, I tried to screen new zebrafish mutants that have defects in DNA demethylation, but my research goal was not achieved. In addition to mutant screening, I found that both activation-induced cytidine deaminase and methyl CpG-binding domain protein 4 do not function in DNA demethylation, and the level of DNA methylation is dynamically changed during development and caudal fin regeneration in zebrafish.

Research Products

• [Journal Article] Decrease in cytosine methylation at CpG island shores and increase in DNA fragmentation during zebrafish aging. (2014)
  • Author(s): Shimoda, N., Izawa, T., Yoshizawa, A., Yokoi, H., Kikuchi, Y. and Hashimoto, N.
  • Journal Title: Age Volume: 36 Pages: 103-115
  • Peer Reviewed
• [Journal Article] Expression patterns of dnmt3aa, dnmt3ab, and dnmt4 during development and fin regeneration in zebrafish. (2014)
  • Author(s): Takayama, K., Shimoda, N., Takanaga, S., Hozumi, S. and Kikuchi, Y.
  • Journal Title: Gene Expression Patterns Volume: 14 Pages: 105-110
  • Peer Reviewed
• [Journal Article] Ddx46 Is Required for Multi-Lineage Differentiation of Hematopoietic Stem Cells in Zebrafish. (2013)
  • Author(s): Hirabayashi, R., Hozumi, S., Higashijima, S. and Kikuchi, Y.
  • Journal Title: Stem Cells and Development Volume: 22 Pages: 2532-2542
  • Peer Reviewed
• [Journal Article] Transient reduction of 5-methylcytosine and 5-hydroxymethylcytosine is associated with active DNA demethylation during regeneration of zebrafish fin. (2013)
  • Author(s): Hirose, K., Shimoda, N. and Kikuchi, Y.
  • Journal Title: Epigenetics Volume: 9 Pages: 899-906
  • Peer Reviewed
• [Journal Article] DEAD-Box Protein Ddx46 Is Required for the Development of the Digestive Organs and Brain in Zebrafish. (2012)
  • Author(s): Hozumi, S., Hirabayashi, R., Yoshizawa, A., Ogata, M., Ishitani, T., Tsutsumi, M., Kuroiwa, A., Itoh, M. and Kikuchi, Y.
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Expression patterns of lgr4 and lgr6 during zebrafish development. (2011)
  • Author(s): Hirose, K., Shimoda, N. and Kikuchi, Y.
  • Journal Title: Gene Expression Patterns Volume: 11 Issue: 7 Pages: 378-383
  • DOI: 10.1016/j.gep.2011.04.002
  • Peer Reviewed
• [Journal Article] Zebrafish Dmrta2 regulates neurogenesis in the telencephalon (2011)
  • Author(s): Yoshizawa A.
  • Journal Title: Genes Cells Volume: 16 Issue: 11 Pages: 1097-1109
  • DOI: 10.1111/j.1365-2443.2011.01555.x
  • Peer Reviewed
• [Presentation] ゼブラフィッシュ原腸陥入期における内胚葉細胞の移動機構 (2011)
  • Author(s): 菊池 裕
  • Organizer: 日本動物学会(招待講演)
  • Place of Presentation: 北海道旭川市
• [Presentation] The DEAD-box protein Ddx46 is involved in pre-mRNA splicing for development of digestive organs and brain in zebrafish. (2011)
  • Author(s): Shunya Hozumi, Ryo Hirabayashi, Akio Yoshizawa, Mitsuko Ogata, Tohru Ishitani, Makiko Tsutsumi, Atsushi Kuroiwa, Motoyuki Itoh, Yutaka Kikuchi
  • Organizer: 日本分子生物学会(招待講演)
  • Place of Presentation: 神奈川県横浜市
• [Presentation] Transient reduction of 5-methylcytosine and 5-hydroxymethylcytosine is caused by active DNA demethylation during regeneration of zebrafish fin.
  • Author(s): Hirose, K., Shimoda, N. and Kikuchi, Y.
  • Organizer: 日本発生生物学会
  • Place of Presentation: 島根県
  • Invited
• [Presentation] Expression patterns of Dnmt4, Dnmt6, and Dnmt8 in zebrafish development.
  • Author(s): Takayama, K., Takanaga, S., Shimoda, N. and Kikuchi, Y.
  • Organizer: 日本発生生物学会
  • Place of Presentation: 島根県
• [Presentation] Ddx46 Is Required for Multi-Lineage Differentiation of Hematopoietic Stem Cells in zebrafish.
  • Author(s): Hirabayashi, R., Hozumi, S., Higashijima, S. and Kikuchi, Y.
  • Organizer: 日本発生生物学会
  • Place of Presentation: 島根県
• [Presentation] ゼブラフィッシュ尾ビレ再生における脱分化機構の解析
  • Author(s): 菊池 裕、廣瀬健太朗、下田修義、髙山和也、塩見太志、穂積俊矢
  • Organizer: 日本解剖学会
  • Place of Presentation: 自治医大
  • Invited
• [Presentation] DEAD-box protein Ddx46 is required for the maintenance of hematopietic stem cells in zebrafish definitive hematopiesis
  • Author(s): Hirabayashi, R., Hozumi, S., and Kikuchi, Y.
  • Organizer: Joint meeting of the 45th JSDB and the 64th JSCB
  • Place of Presentation: 兵庫県神戸市
  • Invited
• [Presentation] ゼブラフィッシュ尾ビレ再生におけるDNAメチル化の変化
  • Author(s): 廣瀬健太朗、下田修義、菊池 裕
  • Organizer: 日本動物学会
  • Place of Presentation: 大阪府豊中市
  • Invited
• [Presentation] The DEAD-box protein Ddx46 is required for differentiation of definitive hematopietic stem cells in zebrafish
  • Author(s): Hirabayashi, R., Hozumi, S., and Kikuchi, Y.
  • Organizer: 日本分子生物学会
  • Place of Presentation: 福岡県福岡市
• [Presentation] 発生過程におけるゼブラフィッシュDnmt4, Dnmt6, Dnmt8の発現パターン
  • Author(s): 高山和也、菊池 裕、高永俊祐、下田修義
  • Organizer: 日本分子生物学会
  • Place of Presentation: 福岡県福岡市
• [Remarks] 広島大学大学院理学研究科生物科学専攻菊池研究室
  • URL: http://home.hiroshima-u.ac.jp/~zebra/index.html