Elucidation of the role of internal DNA sequences in dynamic nucleosome regulation

• Project/Area Number: 18K05556
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38060:Applied molecular and cellular biology-related
• Research Institution: Shimane University
• Principal Investigator: Kato Hiroaki 島根大学, 学術研究院医学・看護学系, 准教授 (40548418)
• Co-Investigator(Kenkyū-buntansha): 浦野 健 島根大学, 学術研究院医学・看護学系, 教授 (70293701)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: ヌクレオソーム / エピジェネティクス / DNA / ヒストン / ソフトウェア / DNA塩基配列 / クロマチン制御

Outline of Final Research Achievements

In order to understand how nucleosomal DNA subsequences affect dynamic nucleosome regulation, we need to have a reliable tool for prediction of nucleosome positioning. In this study, we developed an R/Bioconductor package nuCpos for this purpose and studied the potential of this tool in various aspects. Compared to an MNase-seq-based tool, nuCpos predicts nucleosome positioning with high accuracy. Detailed analyses revealed that the high-resolution of chemical nucleosome maps accounts for appropriate recognition of histone-contact sides of DNA strings. With this tool, users can predict affinity of natural and artificial DNA sequences for nucleosome formation.

Academic Significance and Societal Importance of the Research Achievements

ヒトを含む真核生物の染色体DNAは、ヒストンタンパク質にDNAが巻きついたヌクレオソームを基本単位として核の中に収納されています。ヌクレオソームの配置はエピジェネティクス制御に重要ですが、一見無秩序に並んでいるように見えるDNAの塩基配列が、ヌクレオソームの配置にどう寄与するのかわかっていません。本研究ではDNA配列からヌクレオソーム配置を予測するソフトウェアを開発しました。これは、DNA配列とヌクレオソーム配置の関係や、遺伝的多様性とエピジェネティクスの関係を、さらに詳細に理解するための手がかりになると期待されます。

Research Products

• [Int'l Joint Research] カンザス州立大学(米国)
• [Int'l Joint Research] Cornell University(米国)
• [Int'l Joint Research] Universite de Namur(ベルギー)
• [Journal Article] Chemical map-based prediction of nucleosome positioning using the Bioconductor package nuCpos (2021)
  • Author(s): Kato Hiroaki、Shimizu Mitsuhiro、Urano Takeshi
  • Journal Title: BMC Bioinformatics Volume: 22 Issue: 1 Pages: 322-322
  • DOI: 10.1186/s12859-021-04240-2
  • Peer Reviewed / Open Access
• [Journal Article] Sequence-dependent nucleosome formation in trinucleotide repeats evaluated by in vivo chemical mapping (2021)
  • Author(s): Koji Katsumata, Yuichi Ichikawa, Tomohiro Fuse, Hitoshi Kurumizaka, Akio Yanagida , Takeshi Urano, Hiroaki Kato, Mitsuhiro Shimizu
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 556 Pages: 179-184
  • DOI: 10.1016/j.bbrc.2021.03.155
  • Peer Reviewed / Open Access
• [Journal Article] Gcn2 eIF2α kinase mediates combinatorial translational regulation through nucleotide motifs and uORFs in target mRNAs (2020)
  • Author(s): Chikashige Yuji、Kato Hiroaki、Thornton Mackenzie、Pepper Whitney、Hilgers Madelyn、Cecil Ariana、Asano Izumi、Yamada Haana、Mori Chie、Brunkow Cheyenne、Moravek Carter、Urano Takeshi、Singh Chingakham Ranjit、Asano Katsura
  • Journal Title: Nucleic Acids Research Volume: 48 Issue: 16 Pages: 8977-8992
  • DOI: 10.1093/nar/gkaa608
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ヌクレオソームポジショニングのゲノムワイド解析 (2020)
  • Author(s): 清水光弘、加藤太陽
  • Journal Title: 細胞 Volume: 52(9) Pages: 503-507
  • NAID: 40022426687
• [Journal Article] Chemical map-based prediction of nucleosome positioning using the Bioconductor package nuCpos (2019)
  • Author(s): Kato Hiroaki、Shimizu Mitsuhiro、Urano Takeshi
  • Journal Title: bioRxiv Volume: 2019.12.25 Pages: 888305-888305
  • DOI: 10.1101/2019.12.25.888305
  • Open Access
• [Journal Article] Regulation of ectopic heterochromatin-mediated epigenetic diversification by the JmjC family protein Epe1 (2019)
  • Author(s): Sorida Masato、Hirauchi Takahiro、Ishizaki Hiroaki、Kaito Wataru、Shimada Atsushi、Mori Chie、Chikashige Yuji、Hiraoka Yasushi、Suzuki Yutaka、Ohkawa Yasuyuki、Kato Hiroaki、Takahata Shinya、Murakami Yota
  • Journal Title: PLOS Genetics Volume: 15 Issue: 6 Pages: e1008129-e1008129
  • DOI: 10.1371/journal.pgen.1008129
  • NAID: 120007002166
  • Peer Reviewed / Open Access
• [Journal Article] How does Hsp90 function in RNAi-dependent heterochromatin assembly? (2019)
  • Author(s): Kato H, Okazaki K, Urano T.
  • Journal Title: Current Genetics Volume: 65 Issue: 1 Pages: 87-91
  • DOI: 10.1007/s00294-018-0866-0
  • NAID: 120006648413
  • Peer Reviewed / Open Access
• [Journal Article] Generation and characterization of antagonistic anti-human interleukin (IL)-18 monoclonal antibodies with high affinity: Two types of monoclonal antibodies against full-length IL-18 and the neoepitope of inflammatory caspase-cleaved active IL-18. (2019)
  • Author(s): Nariai Y, Kamino H, Obayashi E, Kato H, Sakashita G, Sugiura T, Migita K, Koga T, Kawakami A, Sakamoto K, Kadomatsu K, Nakakido M, Tsumoto K, Urano T.
  • Journal Title: Archives of Biochemistry and Biophysics Volume: 663 Pages: 71-82
  • DOI: 10.1016/j.abb.2019.01.001
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of ectopic heterochromatin-mediated epigenetic diversification by the JmjC family protein Epe1 (2019)
  • Author(s): Masato Sorida, Takahiro Hirauchi, Hiroaki Ishizaki, Wataru Kaito, Atsushi Shimada, Chie Mori, Yuji Chikashige, Yasushi Hiraoka, Yutaka Suzuki, Yasuyuki Ohkawa, Hiroaki Kato, Shinya Takahata, Yota Murakami
  • Journal Title: Plos Genetics Volume: 印刷中
  • NAID: 120007002166
  • Peer Reviewed / Open Access
• [Journal Article] RNAi-dependent heterochromatin assembly in fission yeast Schizosaccharomyces pombe requires heat-shock molecular chaperones Hsp90 and Mas5. (2018)
  • Author(s): Okazaki K, Kato H, Iida T, Shinmyozu K, Nakayama JI, Murakami Y, Urano T.
  • Journal Title: Epigenetics & Chromatin Volume: 11 Issue: 1 Pages: 26-26
  • DOI: 10.1186/s13072-018-0199-8
  • NAID: 120006651232
  • Peer Reviewed / Open Access
• [Journal Article] Cancer-related transcription regulator protein NAC1 forms a protein complex with CARM1 for ovarian cancer progression. (2018)
  • Author(s): Nakayama N, Sakashita G, Nariai Y, Kato H, Sinmyozu K, Nakayama JI, Kyo S, Urano T, Nakayama K.
  • Journal Title: Oncotarget Volume: 9 Issue: 47 Pages: 28408-28420
  • DOI: 10.18632/oncotarget.25400
  • Peer Reviewed / Open Access
• [Presentation] A chimeric chemical model revealed asymmetric DNA pattern in transcribed nucleosomes (2022)
  • Author(s): Kato H, Shimizu M, Urano T
  • Organizer: The 30th Hot Spring Harbor International Symposium
  • Int'l Joint Research
• [Presentation] ケミカルハイブリッドモデルによるヌクレオソーム配置予測 (2021)
  • Author(s): 加藤太陽、清水光弘、浦野健
  • Organizer: 第93回日本遺伝学会大会
• [Presentation] ケミカルマップに基づくヌクレオソームDNAの相性予測 (2021)
  • Author(s): 加藤太陽、清水光弘、浦野健
  • Organizer: 第１４回エピジェネティクス研究会年会
• [Presentation] 塩基構成から眺めるクロマチン (2019)
  • Author(s): 加藤太陽、浦野健
  • Organizer: 日本遺伝学会第91回大会
• [Presentation] RNA polymerase II高精度解析で迫る転写一時停止とヒストン修飾制御 (2019)
  • Author(s): 梶谷卓也、石井ひとみ、加藤太陽、木村宏、大川恭行、Damien Hermand、John Lis、村上洋太
  • Organizer: 日本遺伝学会第91回大会
• [Presentation] Training a dHMM with a chemical map improved accuracy of nucleosome positioning prediction in yeasts (2018)
  • Author(s): Kato H and Urano T
  • Organizer: Cold Spring Harbor Laboratory Meeting: Epigenetics & Chromatin
  • Int'l Joint Research
• [Remarks] 島根大学医学部病態生化学
  • URL: http://www.shimane-med.ac.jp/biochem2/index.html
• [Remarks] Researchmap
  • URL: https://researchmap.jp/hrk_kato/
• [Remarks] 島根大学医学部病態生化学ホームページ
  • URL: https://www.med.shimane-u.ac.jp/biochem2/
• [Remarks] リサーチマップ
  • URL: https://researchmap.jp/hrk_kato/?lang=japanese
• [Remarks] 島根大学教員情報検索システム
  • URL: https://www.staffsearch.shimane-u.ac.jp/kenkyu/search/e5084ae925c23e6c843da12a5eef8c35/detail?page=research
• [Remarks] 島根大学医学部病態生化学
  • URL: http://www.med.shimane-u.ac.jp/biochem2/index.html