Functional analysis of novel SOX2 complex using in vitro gene transcription system employing genomic DNA as template

• Project/Area Number: 17K07287
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Nagasaki University
• Principal Investigator: NAKAGAWA Takeya 長崎大学, 医歯薬学総合研究科(医学系), 助教 (50363502)
• Co-Investigator(Kenkyū-buntansha): 今村 優子 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (50610937)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 遺伝子転写 / 細胞分化 / クロマチン / 細胞の初期化 / iPS細胞 / 再生医療 / リボソームRNA / クロマチン構造 / 転写調節 / 遺伝子

Outline of Final Research Achievements

SOX2 is one of the genes used to generate iPS cells. Understanding its function is expected to contribute to regenerative medicine. In this project, we performed a functional analysis of novel SOX2 complex. Because TBP is an important gene for gene transcriptional regulation, we focused on TBP among proteins included in the SOX2 complex. We demonstrated that SOX2 and TBP cooperatively activate transcription of ribosomal RNA by using an experimental method that reproduces gene transcription in vitro. It was also revealed that SOX2 and TBP cause structural changes in the region of ribosomal RNA gene transcriptional regulation on the genome. These results revealed that SOX2 regulates ribosomal RNA trnascription.

Academic Significance and Societal Importance of the Research Achievements

細胞の分化を人工的にコントロールし、例えば心筋細胞、脳神経細胞、肝細胞など疾患の治療に利用できる細胞を作製することは国民の健康維持のために非常に有益だと考え得る。本研究課題では細胞の分化を抑える役割を担う遺伝子であるSOX2の機能の一部を明らかにした。この様な細胞分化のコントロールに関する知見を積み重ねていくことが、将来的な細胞や臓器を再生し移植する再生医療の実現へと繋がって行く。

Research Products

• [Journal Article] miR-222 regulates proliferation of primary mouse hepatocytes in vitro. (2019)
  • Author(s): Higashi, M., Yoneda, M., Nakagawa, T., Ikeda, M., and Ito, T.
  • Journal Title: Biochem Biophys Res Commun Volume: 511 Issue: 3 Pages: 644-649
  • DOI: 10.1016/j.bbrc.2019.02.093
  • Peer Reviewed
• [Journal Article] MicroRNA-3662 expression correlates with antiviral drug resistance in adult T-cell leukemia/lymphoma cells. (2018)
  • Author(s): Yasui K, Izumida M, Nakagawa T, Kubo Y, Hayashi H, Ito T, Ikeda H, Matsuyama T
  • Journal Title: Biochem Biophys Res Commun Volume: 印刷中 Issue: 4 Pages: 833-837
  • DOI: 10.1016/j.bbrc.2018.04.159
  • Peer Reviewed / Open Access
• [Journal Article] Defects in centromeric/pericentromeric histone H2A T120 phosphorylation by hBUB1 cause chromosome missegregation producing multinucleated cells (2018)
  • Author(s): Maeda Katsutoshi、Yoneda Mitsuhiro、Nakagawa Takeya、Ikeda Kazuhiro、Higashi Miki、Nakagawa Kaori、Miyakoda Mana、Yui Katsuyuki、Oda Hiroaki、Inoue Satoshi、Ito Takashi
  • Journal Title: Genes to Cells Volume: 23 Issue: 10 Pages: 828-838
  • DOI: 10.1111/gtc.12630
  • Peer Reviewed
• [Journal Article] The MAP3K2-ERK5 pathway upregulates cyclin D1 expression through histone H2A (Thr120) phosphorylation by VRK1 (2018)
  • Author(s): Kato M, Yoneda M, Takeshima Y, Amatya V, Higashi M, Nakagawa T, Ito T
  • Journal Title: Acta medica Nagasakiensia Volume: 62 Pages: 15-26
  • NAID: 130007683941
  • Peer Reviewed
• [Journal Article] Enhancer function regulated by combinations of transcription factors and cofactors (2018)
  • Author(s): Nakagawa Takeya、Yoneda Mitsuhiro、Higashi Miki、Ohkuma Yoshiaki、Ito Takashi
  • Journal Title: Genes to Cells Volume: 23 Issue: 10 Pages: 808-821
  • DOI: 10.1111/gtc.12634
  • Peer Reviewed