Mechanism of neural stem cell maintenance by chromatin regulator

• Project/Area Number: 24613006
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: epigenetics
• Research Institution: Jichi Medical University
• Principal Investigator: TOMINAGA KAORU 自治医科大学, 医学部, 准教授 (20265242)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: エピジェネティクス / クロマチン / 神経幹細胞 / ヒストンアセチル化 / 細胞増殖 / 遺伝子発現 / マウスモデル / モデルマウス

Outline of Final Research Achievements

Epigenetic mechanism via chromatin regulation is crucial for many aspects of biological processes including maintenance of stem cells. MRG15 is the chromodomain-containing and chromatin-binding protein. It is known that MRG15 involves in gene regulation and splicing via making large complexes with other proteins. To investigate the role of MRG15 in neural stem/progenitor cells, we have produced MRG15 deficient mice in which MRG15 was specifically deleted in neural stem/progenitor cells. Although these mice were born in accordance with Mendelian ratio, their body size as well as brain weight was significantly reduced compared with that of control littermates. Moreover, in vitro growth ability of the neural stem/progenitor cells isolated from these mice was strongly suppressed. These results suggest that gene regulation and splicing in which MRG15 involves have a pivotal role in maintenance and function of neural stem/progenitor cells.

Research Products

• [Journal Article] The emerging role of senescent cells in tissue homeostasis and pathophysiology (2015)
  • Author(s): Tominaga, K.
  • Journal Title: Pathobiol Aging Age Relat Dis Volume: 5 Issue: 1 Pages: 27743-27743
  • DOI: 10.3402/pba.v5.27743
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The emerging role of senescent cells in tissue homeostasis and pathophysiology. (2015)
  • Author(s): Tominaga, K.
  • Journal Title: Pathobiol Aging Age Relat Dis. Volume: 5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rapid selection of XO embryonic stem cells using Y chromosome-linked GFP transgenic mice. (2014)
  • Author(s): Yamamoto, S., Nagao, Y., Kuroiwa, K., Hakamata, Y., Ichida, M., Saito-Ohara, F., Tominaga, K., and Endo, H.
  • Journal Title: Transgenic Res. Volume: 23 Issue: 5 Pages: 757-765
  • DOI: 10.1007/s11248-014-9813-0
  • Peer Reviewed
• [Journal Article] Paraneoplastic cerebellar degeneration associated with an onconeural antibody against creatine kinase, brain-type (2013)
  • Author(s): Tetsuka, S. Tominaga, K. Ohta, E. Kuroiwa, K. Sakashita, E. Kasashima, K. Hamamoto, T. Namekawa, M. Morita, M. Natsui, S. Morita, T. Tanaka, K. Takiyama, Y. Nakano, I. Endo, H.
  • Journal Title: J Neurol Sci Volume: 335 Issue: 1-2 Pages: 48-57
  • DOI: 10.1016/j.jns.2013.08.022
  • Peer Reviewed
• [Journal Article] Translational repression of the McKusick-Kaufman syndrome transcript by unique upstream open reading frames encoding mitochondrial proteins with alternative polyadenylation sites (2013)
  • Author(s): Akimoto, C. Sakashita, E., Kasashima, K., Kuroiwa, K., Tominaga, K., Hamamoto, T., and Endo, H.
  • Journal Title: Biochem Biophys Acta Volume: 1830 Issue: 3 Pages: 2728-2738
  • DOI: 10.1016/j.bbagen.2012.12.010
  • Peer Reviewed
• [Journal Article] The role of chromatin reorganization in the process of cellular senescence (2012)
  • Author(s): 冨永 薫
  • Journal Title: Curr Drug Targets Volume: 13 Pages: 1593-1602
  • Peer Reviewed
• [Presentation] Rapid selection of XO embryonic stem cells using Y chromosome-linked GFP transgenic mice (2015)
  • Author(s): 遠藤仁司、山本智、長尾泰光、黒岩憲二、市田勝、冨永薫
  • Organizer: 日本分子生物学会、日本生化学会
  • Place of Presentation: 神戸ポートアイランド（神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 発達段階特異的RNA結合蛋白質Drb1の細胞質封入体形成機構の解析 (2015)
  • Author(s): 益子貴史、坂下英司、笠嶋克巳、黒岩憲二、冨永薫、松浦徹、遠藤仁司
  • Organizer: 日本分子生物学会、日本生化学会
  • Place of Presentation: 神戸ポートアイランド（神戸市）
  • Year and Date: 2015-12-01
• [Presentation] ヒストン修飾によるスプライシング制御が精子形成過程を制御する (2015)
  • Author(s): 岩森巨樹、冨永薫、岩森督子、佐藤哲也、大川恭行、小野悦路、Martin Matzuk
  • Organizer: 日本エピジェネティクス研究会
  • Place of Presentation: 学術総合センター 一橋講堂（東京都千代田区）
  • Year and Date: 2015-05-25
• [Presentation] Chromatin regulator MRG15 is required for spermatogenesis in mice
  • Author(s): Kaoru Tominaga
  • Organizer: The 10th Nikko International Symposium 2013
  • Place of Presentation: Jichi Medical University, Tochigi, JAPAN
  • Invited
• [Remarks] http://www.jichi.ac.jp/biochem/kinou/
• [Remarks] 自治医科大学医学部生化学講座機能生化学部門ホームページ
  • URL: http://www.jichi.ac.jp/biochem/kinou/
• [Remarks] 自治医科大学生化学講座機能生化学部門ホームページ
  • URL: http://www.jichi.ac.jp/biochem/kinou/
• [Remarks] 自治医科大学生化学講座機能生化学部門ホームページ
  • URL: http://www.jichi.ac.jp/biochem/kinou/