Analysis of chromatin dynamics during replication and transcription using permeabilized cells

• Project/Area Number: 17H05013
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Genetics/Chromosome dynamics
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Tachiwana Hiroaki 公益財団法人がん研究会, がん研究所 がん生物部, 研究員 (70546382)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥26,130,000 (Direct Cost: ¥20,100,000、Indirect Cost: ¥6,030,000); Fiscal Year 2019: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2018: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000); Fiscal Year 2017: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
• Keywords: クロマチン / ヒストン / エピジェネティクス / エピジェネティックス

Outline of Final Research Achievements

In eukaryotes, DNA is stored in the cell nucleus by forming a structure called chromatin. Chromatin regulates gene expression, which enables to produce cells with different functions, by changing its structure. A factor that alters the structure of chromatin is the diversity of histones, which are major components of chromatin. The structure and function of chromatin correlate with incorporated histone subtypes (histone variant), which has a similar amino acid sequence to the canonical histone. However, it is not clear how each histone variant is deposited to a specific region of chromatin. In this study, we found that the structure of chromatin regulates histone incorporations.

Academic Significance and Societal Importance of the Research Achievements

本研究は遺伝子発現制御機構に関する重要な因子であるヒストンバリアントが、どのようにしてゲノムDNA中に取り込まれるかを明らかにした。遺伝子発現の異常は多くの疾患の原因となっている。そのため、その制御機構の解明が重要だと考えられている。本研究はゲノムDNAが形成しているクロマチン構造とその構成因子であるヒストンバリアントに着目して、クロマチン構造を介した遺伝子発現制御機構の研究を行なった。本研究の成果は、遺伝子発現制御機構の解明に貢献し、疾患の制御にも繋がる次のアイデアの創出が期待される。

Research Products

• [Journal Article] Nucleosome destabilization by nuclear non-coding RNAs. (2020)
  • Author(s): †Fujita R, †Yamamoto T, Arimura Y, Fujiwara S, Tachiwana H, Ichikawa Y, Sakata S, Yang L, Maruyama R, Hamada M, Nakao M, *Saitoh N, *Kurumizaka H
  • Journal Title: Commun Biol Volume: 3 Issue: 1 Pages: 60-60
  • DOI: 10.1038/s42003-020-0784-9
  • Peer Reviewed / Open Access
• [Journal Article] Cryo-EM Structures of Centromeric Tri-nucleosomes Containing a Central CENP-A Nucleosome. (2020)
  • Author(s): Yoshimasa Takizawa, Cheng-Han Ho, Hiroaki Tachiwana, Hideyuki Matsunami, Wataru Kobayashi, Midori Suzuki, Yasuhiro Arimura, Tetsuya Hori, Tatsuo Fukagawa, Melanie D Ohi, Matthias Wolf, Hitoshi Kurumizaka
  • Journal Title: Structure Volume: 28 Issue: 1 Pages: 44-53
  • DOI: 10.1016/j.str.2019.10.016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Incorporation and influence of Leishmania histone H3 in chromatin (2019)
  • Author(s): Dacher Mariko、Tachiwana Hiroaki、Horikoshi Naoki、Kujirai Tomoya、Taguchi Hiroyuki、Kimura Hiroshi、Kurumizaka Hitoshi
  • Journal Title: Nucleic Acids Research Volume: 47 Issue: 22 Pages: 11637-11648
  • DOI: 10.1093/nar/gkz1040
  • Peer Reviewed / Open Access
• [Journal Article] The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism. (2019)
  • Author(s): Arimura Y, Tachiwana H, Takagi H, Hori T, Kimura H, Fukagawa T, Kurumizaka H
  • Journal Title: Nature Commun. Volume: 10 Issue: 1 Pages: 576-576
  • DOI: 10.1038/s41467-019-08314-x
  • Peer Reviewed / Open Access
• [Journal Article] Histone H2A variants confer specific properties to nucleosomes and impact on chromatin accessibility (2018)
  • Author(s): Osakabe Akihisa、Lorkovic Zdravko J、Kobayashi Wataru、Tachiwana Hiroaki、Yelagandula Ramesh、Kurumizaka Hitoshi、Berger Frederic
  • Journal Title: Nucleic Acids Research Volume: 46 Issue: 15 Pages: 7675-7685
  • DOI: 10.1093/nar/gky540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 高次クロマチン構造依存的なヒストン取り込み機構 (2019)
  • Author(s): 立和名博昭、ダッシェマリコ、前原一満、原田哲仁、大川恭行、木村宏、胡桃坂仁志、斉藤典子
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Analyzing H2A.Z functions in cancer progression (2019)
  • Author(s): Tachiwana H, Ueda K, Kurumizaka H, Saitoh N
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] クロマチン高次構造によるヒストンの取り込み制御機構 (2019)
  • Author(s): 立和名博昭、ダッシェマリコ、前原一満、原田哲仁、大川恭行、木村宏、胡桃坂仁志、斉藤典子
  • Organizer: 第92回日本生化学会大会
• [Presentation] Analysis of histone incorporation at the DNA sequence-level using permeabilized cells and reconstituted histone complexes. (2019)
  • Author(s): Tachiwana H, Dacher M, Harada A, Maehara K, Ohkawa Y, Kimura H, Kurumizaka H, Saitoh N
  • Organizer: EMBO Workshop: Chromatin and Epigenetics
  • Int'l Joint Research
• [Presentation] Analysis of histone dynamics using permeabilized cells and reconstituted histone complexes (2018)
  • Author(s): Hiroaki Tachiwana, Hiroshi Kimura, Hitoshi Kurumizaka, Noriko Saitoh
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] クロマチンの高次構造とヒストンダイナミクスの解析 (2018)
  • Author(s): 立和名 博昭、ダッシェ マリコ、原田哲仁、木村宏、大川恭行、胡桃坂仁志、斉藤典子
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Structural analysis of the centromere specific nucleosome. (2017)
  • Author(s): Hiroaki Tachiwana, Midori Suzuki, Yoshimasa Takizawa, Matthias Wolf, Hitoshi Kurumizaka
  • Organizer: 第55回日本生物物理学会年会
• [Presentation] 透過性細胞と再構成ヒストン複合体によるヒストン動態の解析 (2017)
  • Author(s): 立和名博昭、原田哲仁、大川恭行、木村宏、斉藤典子、胡桃坂仁志
  • Organizer: 第40回日本分子生物学会年会
• [Book] 実験医学別冊 あなたのタンパク質精製、大丈夫ですか？ 貴重なサンプルをロスしないための達人の技 (2018)
  • Author(s): 立和名博昭
  • Total Pages: 186
  • Publisher: 羊土社
  • ISBN: 9784758122382