Study of genome maintenance / inheritance mechanism based on chromosome 4D structure analysis

• Project/Area Number: 15H02369
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Genome biology
• Research Institution: The University of Tokyo
• Principal Investigator: SHIRAHIGE KATSUHIKO 東京大学, 分子細胞生物学研究所, 教授 (90273854)
• Co-Investigator(Kenkyū-buntansha): 須谷 尚史 東京大学, 分子細胞生物学研究所, 講師 (30401524)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥43,420,000 (Direct Cost: ¥33,400,000、Indirect Cost: ¥10,020,000); Fiscal Year 2017: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000); Fiscal Year 2016: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000); Fiscal Year 2015: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
• Keywords: 染色体高次構造 / 細胞周期 / コンデンシン / コヒーシン / 機械学習 / 染色体 / 染色体構築原理 / 次世代シークエンサー / ゲノム維持

Outline of Final Research Achievements

For this study, we have introduced in situ Hi-C method to explore 3D and 4D structure of genome. Omics analysis pipeline that integrates Hi-C, ChIP-seq, Trasncriptome, and Genome sequence data has been developed and help us to visualize chromosome functional structures at various level. Using this pipeline, the transition of the high order structure of chromosome during cell cycle was captured. Notable achievements include 1) Condensin is important for re-annealing of single-stranded DNA generated during transcription, which activity is important for chromosome condensation, b) Two cohesin acetyltransferases (ESCO 1 and 2) in human function in different pathways. 1 induces sisterchromatids cohesion throughout the cell cycle, while 2 travels on chromosomes together with DNA helicase during replication, and this interaction with helicase prevent degradation of Esco2. c) Origin of DNA replication of the fission yeast genome is determined by three factors as revealed by machine learning.

Research Products

• [Int'l Joint Research] オックスフォード大学/クリック研究所(英国)
• [Int'l Joint Research] ペンシルバニア大学/フィラデルフィアこども病院(米国)
• [Int'l Joint Research] カロリンスカ研究所(スウェーデン)
• [Journal Article] DBTSS/DBKERO for integrated analysis of transcriptional regulation (2018)
  • Author(s): Suzuki Ayako、Kawano Shin、Mitsuyama Toutai、Suyama Mikita、Kanai Yae、Shirahige Katsuhiko、Sasaki Hiroyuki、Tokunaga Katsushi、Tsuchihara Katsuya、Sugano Sumio、Nakai Kenta、Suzuki Yutaka
  • Journal Title: Nucleic Acids Research Volume: 46 Issue: (D1) Pages: D229-D238
  • DOI: 10.1093/nar/gkx1001
  • Peer Reviewed / Open Access
• [Journal Article] Statistical Analysis and Quality Assessment of ChIP-seq Data with DROMPA. (2018)
  • Author(s): Nakato R, Shirahige K.
  • Journal Title: Methods Mol Biol. Volume: 1672 Pages: 631-643
  • DOI: 10.1007/978-1-4939-7306-4_41
  • ISBN: 9781493973057, 9781493973064
  • Peer Reviewed
• [Journal Article] interleukin-11 induces and maintains progenitors of different cell lineages during Xenopus tadpole tail regeneration (2017)
  • Author(s): Tsujioka Hiroshi、Kunieda Takekazu、Katou Yuki、Shirahige Katsuhiko、Fukazawa Taro、Kubo Takeo
  • Journal Title: Nature Comunications Volume: 8 Issue: 1 Pages: 495-495
  • DOI: 10.1038/s41467-017-00594-5
  • Peer Reviewed / Open Access
• [Journal Article] An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells. (2017)
  • Author(s): Koui Y, Kido T, Ito T, Oyama H, Chen SW, Katou Y, Shirahige K, Miyajima A.
  • Journal Title: Stem Cell Reports. Volume: 9 Issue: 2 Pages: 490-498
  • DOI: 10.1016/j.stemcr.2017.06.010
  • Peer Reviewed / Open Access
• [Journal Article] Genome-Wide Target Analyses of Otx2 Homeoprotein in Postnatal Cortex (2017)
  • Author(s): Sakai Akiko、Nakato Ryuichiro、Ling Yiwei、Hou Xubin、Hara Norikazu、Iijima Tomoya、Yanagawa Yuchio、Kuwano Ryozo、Okuda Shujiro、Shirahige Katsuhiko、Sugiyama Sayaka
  • Journal Title: Frontiers in Neuroscience Volume: 11 Pages: 307-307
  • DOI: 10.3389/fnins.2017.00307
  • Peer Reviewed / Open Access
• [Journal Article] Rtt101-Mms1-Mms22 coordinates replication-coupled sister chromatid cohesion and nucleosome assembly (2017)
  • Author(s): Zhang J, Shi D, Li X, Ding L, Tang J, Liu C, Shirahige K, Cao Q, Lou H.
  • Journal Title: EMBO Rep. Volume: 18 Issue: 8 Pages: 1294-1305
  • DOI: 10.15252/embr.201643807
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Decreased cohesion in the brain leads to defective synapse development and anxiety-related behavior (2017)
  • Author(s): Fujita Y, Masuda K, Bando M, Nakato R, Katou Y, Tanaka T, Nakayama M, Takao K, Miyakawa T, Tanaka T, Ago Y, Hashimoto H, Shirahige K, Yamashita T.
  • Journal Title: J. Exp. Med. Volume: 印刷中 Issue: 5 Pages: 1431-1452
  • DOI: 10.1084/jem.20161517
  • Peer Reviewed / Open Access
• [Journal Article] Cornelia de Lange syndrome and molecular implications of the cohesin complex: Abstracts from the 7th biennial scientific and educational symposium 2016. (2017)
  • Author(s): Kline AD, Krantz ID, Deardorff MA, Shirahige K, Dorsett D, Gerton JL, Wu M, Mehta D, Mills JA, Carrico CS, Noon S, Herrera PS, Horsfield JA, Bettale C, Morgan J, Huisman SA, Moss J, McCleery J, Grados M, Hansen BD, Srivastava S, Taylor-Snell E, Kerr LM, Katz O, Calof AL, Musio A, Egense A, Haaland RE.
  • Journal Title: Am J Med Genet A. Volume: 173(5) Issue: 5 Pages: 1172-1185
  • DOI: 10.1002/ajmg.a.38161
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ChIP-seq Analysis of Condensin Complex in Cultured Mammalian Cells. (2017)
  • Author(s): Sakata T, Shirahige K, Sutani T.
  • Journal Title: Methods Mol Biol. Volume: 1515 Pages: 257-271
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ASBEL-TCF3 complex is required for the tumorigenicity of colorectal cancer cells. (2016)
  • Author(s): Taniue K, Kurimoto A, Takeda Y, Nagashima T, Okada-Hatakeyama M, Yuki K, Katsuhiko S, Akiyama T.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 113 Issue: 45 Pages: 12739-12744
  • DOI: 10.1073/pnas.1605938113
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MYU, a Target lncRNA for Wnt/c-Myc Signaling, Mediates Induction of CDK6 to Promote Cell Cycle Progression. (2016)
  • Author(s): Kawasaki Y, Komiya M, Matsumura K, Negishi L, Suda S, Okuno M, Yokota N, Osada T, Nagashima T, Hiyoshi M, Okada-Hatakeyama M, Kitayama J, Shirahige K, Akiyama T.
  • Journal Title: Cell Rep. Volume: 16(10) Issue: 10 Pages: 2554-64
  • DOI: 10.1016/j.celrep.2016.08.015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ARCN1 Mutations Cause a Recognizable Craniofacial Syndrome Due to COPI-Mediated Transport Defects. (2016)
  • Author(s): Izumi K, Brett M, Nishi E, Drunat S, Tan ES, Fujiki K, Lebon S, Cham B, Masuda K, Arakawa M, Jacquinet A, Yamazumi Y, Chen ST, Verloes A, Okada Y, Katou Y, Nakamura T, Akiyama T, Gressens P, Foo R, Passemard S, Tan EC, El Ghouzzi V, Shirahige K.
  • Journal Title: Am J Hum Genet. Volume: 99(2) Issue: 2 Pages: 451-9
  • DOI: 10.1016/j.ajhg.2016.06.011
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] DNMT3A R882 mutants interact with polycomb proteins to block haematopoietic stem and leukaemic cell differentiation. (2016)
  • Author(s): Koya J, Kataoka K, Sato T, Bando M, Kato Y, Tsuruta-Kishino T, Kobayashi H, Narukawa K, Miyoshi H, Shirahige K, Kurokawa M.
  • Journal Title: Nat Commun. Volume: 7 Issue: 1 Pages: 10924-10924
  • DOI: 10.1038/ncomms10924
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Recent advances in ChIP-seq analysis: from quality management to whole-genome annotation. (2016)
  • Author(s): Nakato R, Shirahige K.
  • Journal Title: Brief Bioinform Volume: 12 Pages: 1-12
  • DOI: 10.1093/bib/bbw023
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Rif1 binds to G-quadruplexes and suppresses replication over long distances. (2015)
  • Author(s): Yutaka Kanoh, Seiji Matsumoto, Rino Fukatsu, Naoko Kakusho, Nobuaki Kono, Claire Renard-Guillet, Koji Masuda, Keisuke Iida, Kazuo Nagasawa, Katsuhiko Shirahige, and *Hisao Masai
  • Journal Title: Nature Struct. Mol. Biol. Volume: 22 Issue: 11 Pages: 889-897
  • DOI: 10.1038/nsmb.3102
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Deubiquitinating Enzyme USP7 Regulates Androgen Receptor Activity by Modulating Its Binding to Chromatin (2015)
  • Author(s): Shu-Ting Chen, Maiko Okada, Ryuichiro Nakato, Kosuke Izumi, Masashige Bando and Katsuhiko Shirahige
  • Journal Title: Journal of Biological Chemistry Volume: 290 Issue: 35 Pages: 21713-21723
  • DOI: 10.1074/jbc.m114.628255
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Transcriptional regulation by cohesin and its loader (2017)
  • Author(s): Katsuhiko Shirahige
  • Organizer: 第9回NAGOYAグローバルリトリート
  • Place of Presentation: 愛知健康プラザ、愛知県大府市
  • Year and Date: 2017-02-10
  • Int'l Joint Research / Invited
• [Presentation] Organization of 3D genome structure mediated by cohesin and CTCF (2017)
  • Author(s): Toyonari Sakata, Katsuhiko Shirahige
  • Organizer: EMBO Workshop “Evolution in the Time of Genome Architecture”
  • Int'l Joint Research / Invited
• [Presentation] Analysis of human chromosome organization mediated by cohesin complex (2017)
  • Author(s): Toyonari Sakata, Katsuhiko Shirahige
  • Organizer: Genetic Networks (GN) Workshop
  • Int'l Joint Research / Invited
• [Presentation] コヒーシンと染色体の高次機能 (2017)
  • Author(s): Toyonari Sakata, Katsuhiko Shirahige
  • Organizer: 第76回日本癌学会学術総会
  • Invited
• [Presentation] Genetic Link of Human Rare Diseases Identify Regulatory Mechanism of Transcription by Cohesin and its Loader (2016)
  • Author(s): Katsuhiko Shirahige
  • Organizer: CIFAR Genetic Network Workshop
  • Place of Presentation: カナダ、トロント
  • Year and Date: 2016-04-15
  • Int'l Joint Research / Invited
• [Presentation] コヒーシンローダーNIPBLによる転写制御 (2016)
  • Author(s): 白髭克彦
  • Organizer: 第33回染色体ワークショップ 第14回核ダイナミクス研究会
  • Place of Presentation: 宮城県宮城郡松島町
  • Year and Date: 2016-01-13
  • Invited
• [Presentation] How cohesin and its loader regulate transcription? Clues from newly identi ed disease andin vitro reconstitution system (2016)
  • Author(s): Katsuhiko Shirahige
  • Organizer: トロント大学のセミナー
  • Place of Presentation: カナダ、トロント
  • Invited
• [Presentation] コヒーシンローダー、コヒーシンによる転写伸長制御 (2015)
  • Author(s): 白髭克彦
  • Organizer: 第23回 DNA複製・組換え・修復ワークショップ
  • Place of Presentation: 静岡県焼津市
  • Year and Date: 2015-10-19
  • Invited