Molecular mechanism of heterochromatin patterning involved in gene regulation

• Project/Area Number: 18K14675
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Osaka University (2019); The University of Tokushima (2018)
• Principal Investigator: Maeda Ryo 大阪大学, 生命機能研究科, 特別研究員(PD) (90814575)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ヘテロクロマチン / HP1 / H3K9メチル化 / レトロトランスポゾン / 転写制御

Outline of Final Research Achievements

Eukaryotic DNA is wrapped around a protein called histone. Heterochromatin, which is a highly condensed histone-DNA structure and represents a repressive state of gene expression, is essential for maintaining cell identity. In this study, I aimed to elucidate the underlying mechanism of heterochromatin formation. I focused on HP1, which is a component protein of heterochromatin, and clarified its molecular function using knockout analysis.

Academic Significance and Societal Importance of the Research Achievements

哺乳類にはおよそ30000の遺伝子が存在するが、細胞ごとに発現する遺伝子は異なる。本研究は、不必要な遺伝子をいかに発現させない状態にするか、ということに着目し、その状態の形成に必要なタンパク質の機能を明らかにした。この研究成果は、生物の発生や、遺伝子発現異常によって引き起こされるがんなどの病気に対して、根本的な知見をもたらすことが期待できる。

Research Products

• [Journal Article] TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression. (2019)
  • Author(s): Okashita N, Kuroki S, Maeda R, *Tachibana M.
  • Journal Title: Sci Rep. Volume: 9 Issue: 1 Pages: 13462-13462
  • DOI: 10.1038/s41598-019-50058-7
  • Peer Reviewed / Open Access
• [Journal Article] Combined loss of JMJD1A and JMJD1B reveals critical roles for H3K9 demethylation in the maintenance of embryonic stem cells and early embryogenesis. (2018)
  • Author(s): Kuroki, S., Nakai, Y., Maeda, R., Okashita, N., Akiyoshi, M., Yamaguchi, Y., Kitano, S., Miyachi, H., Nakato, R., Ichiyanagi, K., Shirahige, K., Kimura, H., Shinkai, Y., and Tachibana, M.
  • Journal Title: Stem Cell Rep. Volume: 10 Issue: 4 Pages: 1340-1354
  • DOI: 10.1016/j.stemcr.2018.02.002
  • NAID: 120006463740
  • Peer Reviewed / Open Access
• [Presentation] H3K9メチル化hubとしてはたらくHP1の機能 (2019)
  • Author(s): 前田 亮
  • Organizer: 日本分子生物学会年会