Mechanism of the maintenance of functions and structure of chromosome ends

• Project/Area Number: 17H03606
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Genome biology
• Research Institution: The University of Tokyo (2019-2020); Osaka University (2017-2018)
• Principal Investigator: Kanoh Junko 東京大学, 大学院総合文化研究科, 教授 (10323809)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: テロメア / サブテロメア / 染色体 / クロマチン / ゲノムDNA / 重複配列 / タンパク質 / ヒストン / ヘテロクロマチン

Outline of Final Research Achievements

Telomeres at chromosome ends possess repetitive DNA sequences and play essential roles in life maintenance, such as protection of chromosome ends and regulation of cell senescence. Subtelomere, a telomere-adjacent domain, is a uncultivated land in chromosomes due to various technical difficulties due to its incomplete DNA sequence information and its complex mosaic structure with multiple long common sequences. In this study, we investigated the molecular mechanisms for (1) how subtelomeric chromatin structure is formed and (2) how the boundary between a subtelomere and its adjacent euchromatin is regulated.

Academic Significance and Societal Importance of the Research Achievements

近年飛躍的に知見が蓄積したテロメア研究とは対照的に、サブテロメア研究はまだ黎明期に留まっている。本研究は、遺伝学的解析が容易な分裂酵母の利点を活かし、世界に先駆けてサブテロメアの制御や機能を明らかにするものである。また、サブテロメア構造の異常によってサブテロメア微細構造異常症や筋ジストロフィが発症することが知られている。いずれの場合もサブテロメアに存在する遺伝子の発現量の異常が直接的原因とされるが、現在のところ、この病気に対する根本的な治療法はない。本研究によって、サブテロメアにおけるクロマチン構造や遺伝子発現維持機構の詳細が明らかになり、治療法の開発につながることが期待される。

Research Products

• [Int'l Joint Research] 上海国立蛋白質科学研究所(中国)
• [Journal Article] Complete sequences of Schizosaccharomyces pombe subtelomeres reveal multiple patterns of genome variation. (2021)
  • Author(s): Oizumi, Y., Kaji, T., Tashiro, S., Takeshita, Y., Date, Y., and Kanoh, J.
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 611-611
  • DOI: 10.1038/s41467-020-20595-1
  • Peer Reviewed / Open Access
• [Journal Article] Telomere DNA length-dependent regulation of DNA replication timing at internal late replication origins. (2019)
  • Author(s): Hasegawa Y., Yamamoto M., Miyamori J., Kanoh J.
  • Journal Title: Sci. Rep. Volume: 9 Issue: 1 Pages: 9946-9946
  • DOI: 10.1038/s41598-019-46229-1
  • Peer Reviewed / Open Access
• [Journal Article] Casein kinase 2 regulates telomere protein complex formation through Rap1 phosphorylation. (2019)
  • Author(s): Inoue H, Horiguchi M, Ono K, Kanoh J.
  • Journal Title: Nucleic Acids Res. Volume: 47 Issue: 13 Pages: 6871-6884
  • DOI: 10.1093/nar/gkz458
  • Peer Reviewed / Open Access
• [Journal Article] Structural insights into chromosome attachment to the nuclear envelope by an inner nuclear membrane protein Bqt4 in fission yeast. (2019)
  • Author(s): Hu C., Inoue H., Sun W., Takeshita Y., Huang Y., Xu Y., Kanoh J., and Chen Y.
  • Journal Title: Nucleic Acids Res. Volume: 47 Issue: 3 Pages: 1573-1584
  • DOI: 10.1093/nar/gky1186
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Inner Nuclear Membrane Protein Bqt4 in Fission Yeast Contains a DNA-Binding Domain Essential for Telomere Association with the Nuclear Envelope. (2019)
  • Author(s): Hu C., Inoue H., Sun W., Takeshita Y., Huang Y., Xu Y., Kanoh J., and Chen Y.
  • Journal Title: Structure Volume: 27 Issue: 2 Pages: 335-343
  • DOI: 10.1016/j.str.2018.10.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] サブテロメアはゲノム進化のホットスポットである (2021)
  • Author(s): 加納純子
  • Organizer: 第38回染色体ワークショップ
• [Presentation] Complete sequences of S. pombe subtelomeres reveal multiple patterns of genome vari (2020)
  • Author(s): 加納純子
  • Organizer: 第４３回日本分子生物学会年会
  • Int'l Joint Research / Invited
• [Presentation] サブテロメアはゲノム進化のホットスポットである (2020)
  • Author(s): 加納純子
  • Organizer: 第53回酵母遺伝学フォーラム
• [Presentation] Casein kinase 2 (CK2) regulates telomere protein complex formation through Rap1 phosphorylation. (2019)
  • Author(s): Junko Kanoh
  • Organizer: Pombe 2019
  • Int'l Joint Research / Invited
• [Presentation] 染色体末端サブテロメア領域の新規機能制御 (2019)
  • Author(s): 加納純子
  • Organizer: 蛋白研セミナー「細胞運命を決定する核空間制御」
  • Invited
• [Presentation] サブテロメアクロマチン構造の形成機構 (2019)
  • Author(s): 加納純子
  • Organizer: 第４２回日本分子生物学会年会ワークショップ
  • Invited
• [Presentation] サブテロメア全DNA配列決定によって見えてくるサブテロメアDNA構造のダイナミズム (2019)
  • Author(s): 加納純子
  • Organizer: 酵母ルネッサンス2019
  • Invited
• [Presentation] サブテロメア全DNA配列決定により明らかになった２つのsequence variationモード (2019)
  • Author(s): 加納純子
  • Organizer: 第３７回染色体ワークショップ
• [Presentation] New insights into telomeres and subtelomeres in S. pombe (2019)
  • Author(s): Junko Kanoh
  • Organizer: Regulation of Quiescent and Proliferative Pombe Chromatin and Genome
  • Int'l Joint Research / Invited
• [Presentation] サブテロメアクロマチン構造形成の分子機構 (2019)
  • Author(s): 加納純子
  • Organizer: 染色体研究の最前線2019
  • Invited
• [Presentation] Telomere length-dependent regulation of DNA replication timing at non-telomeric regions. (2018)
  • Author(s): Yudai Hasegawa, Junki Miyamori, and Junko Kanoh
  • Organizer: Telomere biology in health and human disease
  • Int'l Joint Research
• [Presentation] 染色体末端領域の新規機能を探る (2018)
  • Author(s): 加納純子
  • Organizer: 蛋白研セミナー「細胞核とクロマチン構造が操る高次生命現象」
  • Invited
• [Presentation] Elucidation of subtelomere functions using S. pombe (2018)
  • Author(s): Junko Kanoh
  • Organizer: 日本遺伝学会第９０回大会
  • Int'l Joint Research / Invited
• [Presentation] 染色体末端による染色体全体の構造・動態制御 (2018)
  • Author(s): 加納純子
  • Organizer: 第４１回日本分子生物学会年会
  • Int'l Joint Research / Invited