Regulation of bacterial phenotypes through histone code of intrinsically-disordered protein

• Project/Area Number: 17K08823
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Niigata University
• Principal Investigator: Nishiyama Akihito 新潟大学, 医歯学系, 講師 (80452069)
• Co-Investigator(Kenkyū-buntansha): 吉田 豊 新潟大学, 医歯学総合研究科, 客員研究員 (40182795)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 結核 / 抗酸菌 / ヒストン様蛋白質 / 天然変性領域 / 結核菌 / 天然変性蛋白質 / 形質制御 / 細菌 / 感染症 / 蛋白質 / 発現制御

Outline of Final Research Achievements

Mycobacterial HU has a histone-like intrinsically-disordered region (C-IDR). In this study, we aimed to elucidate the regulatory mechanism of mycobacterial HU functions through the modulation of C-IDR function. C-IDR is essential for mycobacterial HU functions. In this study, we elucidated C-IDR structure/function relationship, employing various HU mutants. We also investigated the regulatory mechanism of C-IDR functions. Furthermore, HU-dependent gene regulation in mycobacterial species was comprehensively determined by transcriptome analysis of HU-knockout or -knockdown mutants. Our data and future investigation contribute to reveal the regulation of chromosome functions through HU-mediated DNA compaction in mycobacteria and its significance in mycobacterial virulence.

Academic Significance and Societal Importance of the Research Achievements

真核細胞のヒストンとは異なり、原核細胞である細菌では天然変性領域を持つヒストン様蛋白質は希であり、その翻訳後修飾を介したエピジェネティクス制御もほとんど報告されていない。本研究において解析した、従来の細菌HUとは全く異なる抗酸菌HU独自の天然変性領域を介したDNA凝集過程、及びその制御機構は、細菌ヒストン様蛋白質による染色体制御に全く新しい概念をもたらすものであり、学術的意義が高い。また、HUは結核菌の必須蛋白質で、重要な病原性の一つである菌の休眠に関与しており、本研究成果は社会的重要度の高い結核（及びその他の抗酸菌症）の創薬など、新規制御法開発に貢献する。

Research Products

• [Journal Article] Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions. (2017)
  • Author(s): Enany S, Yoshida Y, Tateishi Y, Ozeki Y, Nishiyama A, Savitskaya A, Yamaguchi T, Ohara Y, Yamamoto T, Ato M, Matsumoto S.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 6810-6810
  • DOI: 10.1038/s41598-017-06480-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Conditional control of mycobacterial DNA-binding protein 1 expression in mycobacteria (2018)
  • Author(s): Anna Savitskaya、西山晃史、松本壮吉
  • Organizer: 第91回日本細菌学会総会（福岡）
• [Presentation] Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions (2018)
  • Author(s): Shymaa Enany, Yutaka Yoshida, Yoshitaka Tateishi, Yuriko Ozeki, Akihito Nishiyama, Anna Savitskaya, Takehiro Yamaguchi, Yukiko Ohara, Tadashi Yamamoto, Manabu Ato, Sohkichi Matsumoto
  • Organizer: 第52回日米医学抗酸菌専門部会（The 52nd US-Japan Mycobacteria Panel Meeting 2018 in Niigata）
  • Int'l Joint Research
• [Presentation] The analysis of mycobacterial DNA-binding protein 1 function in mycobacteria using conditional expression system (2017)
  • Author(s): Anna Savitskaya、西山晃史、松本壮吉
  • Organizer: 第2回抗酸菌研究会
• [Presentation] 抗酸菌の長期生存とヒストン様核様体結合タンパク質によるグローバルな細胞機能制御 (2017)
  • Author(s): 西山晃史、Shymaa Enany、Anna Savitskaya、吉田 豊、山本 格、阿戸 学、松本壮吉
  • Organizer: 第54回日本細菌学会中部支部総会（名古屋）