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Search for a pioneer polymerase complex that opens chromatin in non-coding RNA transcribed regions

Research Project

Project/Area Number 21K19235
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionTokyo Metropolitan University

Principal Investigator

Hirota Kouji  東京都立大学, 理学研究科, 教授 (00342840)

Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords非コードRNA / クロマチン / 転写 / 組換え / 減数分裂 / 分裂酵母 / 相同組換え / RNAポリメラーゼ
Outline of Research at the Start

パイオニアポリメラーゼ仮説:「非コードRNAを転写するポリメラーゼがパイオニアとしてその通過領域のクロマチン構造を緩める」の分裂酵母ゲノムでの染色体機能(転写、修復、相同組換えなど)調節における普遍的機能を解明するとともに、パイオニアポリメラーゼ複合体を構成するタンパク質を探索・同定することで、パイオニアポリメラーゼによるクロマチン制御メカニズムの全貌解明を目指す。

Outline of Final Research Achievements

Although noncoding RNA transcription has been found in a variety of organisms and is assumed to have essential functions in life, the functions of most noncoding RNAs are unknown. We have discovered a noncoding RNA, mlonRNA, in the upstream region of the fission yeast fbp1 gene, and found a chromatin remodeling phenomenon by this RNA transcription and a transcription activation mechanism associated with this mlonRNA expression mediated chromatin remodeling. In this study, we elucidate that the regulation by this noncoding RNA is a universal mechanism involved not only in transcription but also in the regulation of various DNA-based reactions such as genome-wide recombination.

Academic Significance and Societal Importance of the Research Achievements

この研究により、減数分裂期組換えを誘導する配偶子形成時における環境ストレスが非コードRNA転写のパターンに影響し、ゲノム上の組換え部位の分布に影響を与えうることを示唆できた。また、mlonRNAは転写のみならず組換え制御にも関与する、グローバルな染色体機能の制御システムの一翼をなすことを示唆できた。この成果から、進化に寄与する減数分裂期組み換えによる遺伝子の多様化現象において、その配偶子を形成するときのストレス環境で機能する遺伝子近傍により大きくバイアスした組換えによる多様化が引き起こされ、効率的な遺伝子進化に寄与している可能性が考えられ、遺伝子機能の進化の新しい可能性を示唆できた。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (27 results)

All 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (15 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 15 results,  Open Access: 11 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Int'l Joint Research] ボストン大学(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] ボストン大学(米国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Application of neural network-based image analysis to detect sister chromatid cohesion defects2023

    • Author(s)
      Ikemoto Daiki、Taniguchi Tomoya、Hirota Kouji、Nishikawa Kiyoshi、Okubo Kan、Abe Takuya
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 2133-2135

    • DOI

      10.1038/s41598-023-28742-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lestaurtinib induces DNA damage that is related to estrogen receptor activation2023

    • Author(s)
      Ooka Masato、Yang Shu、Zhang Li、Kojima Kota、Huang Ruili、Hirota Kouji、Takeda Shunichi、Xia Menghang
    • Journal Title

      Current Research in Toxicology

      Volume: 4 Pages: 100102-100104

    • DOI

      10.1016/j.crtox.2022.100102

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multi-Layered Regulations on the Chromatin Architectures: Establishing the Tight and Specific Responses of Fission Yeast fbp1 Gene Transcription2022

    • Author(s)
      Asada Ryuta、Hirota Kouji
    • Journal Title

      Biomolecules

      Volume: 12 Issue: 11 Pages: 1642-1645

    • DOI

      10.3390/biom12111642

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation Mechanisms of Meiotic Recombination Revealed from the Analysis of a Fission Yeast Recombination Hotspot ade6-M262022

    • Author(s)
      Hirota Kouji
    • Journal Title

      Biomolecules

      Volume: 12 Issue: 12 Pages: 1716-1726

    • DOI

      10.3390/biom12121761

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] XRCC1 counteracts poly(ADP ribose)polymerase (PARP) poisons, olaparib and talazoparib, and a clinical alkylating agent, temozolomide, by promoting the removal of trapped PARP1 from broken DNA.2022

    • Author(s)
      Hirota Kouji、Ooka Masato、Shimizu Naoto、Yamada Kousei、Tsuda Masataka、Ibrahim Mahmoud Abdelghany、Yamada Shintaro、Sasanuma Hiroyuki、Masutani Mitsuko、Takeda Shunichi
    • Journal Title

      Genes to Cells

      Volume: in press Issue: 5 Pages: 331-344

    • DOI

      10.1111/gtc.12929

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A high-throughput 384-well CometChip platform reveals a role for 3-methyladenine in the cellular response to etoposide-induced DNA damage.2022

    • Author(s)
      Li, J., A. Beiser, N. B. Dey, S. Takeda, L. K. Saha, K. Hirota, L. L. Parker, M. Carter, M. I. Arrieta, and R. W. Sobol
    • Journal Title

      NAR Genom Bioinform

      Volume: 4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SPRTN and TDP1/TDP2 Independently Suppress 5-Aza-2′-deoxycytidine-Induced Genomic Instability in Human TK6 Cell Line2022

    • Author(s)
      Nakano Toshiaki,Moriwaki Takahito,Tsuda Masataka,Miyakawa Misa,Hanaichi Yuto,Sasanuma Hiroyuki,Hirota Kouji,Kawanishi Masanobu,Ide Hiroshi,Tano Keizo,Bessho Tadayoshi
    • Journal Title

      Chemical Research in Toxicology

      Volume: 35 Issue: 11 Pages: 2059-2067

    • DOI

      10.1021/acs.chemrestox.2c00213

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Construction of a human hTERT RPE-1 cell line with inducible Cre for editing of endogenous genes2022

    • Author(s)
      N.L. Hindul, A. Jhita, D.G. Oprea, T.A. Hussain, O. Gonchar, M.A.M. Campillo, L. O'Regan, M.T. Kanemaki, A.M. Fry, K. Hirota, K. Tanaka
    • Journal Title

      Biol Open

      Volume: 11 Issue: 2

    • DOI

      10.1242/bio.059056

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Targeting chromosome trisomy for chromosome editing2021

    • Author(s)
      T. Abe, Y. Suzuki, T. Ikeya, K. Hirota
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 18054-18054

    • DOI

      10.1038/s41598-021-97580-1

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] XRCC1 prevents toxic PARP1 trapping during DNA base excision repair2021

    • Author(s)
      Demin Annie A.、Hirota Kouji、Tsuda Masataka、Adamowicz Marek、Hailstone Richard、Brazina Jan、Gittens William、Kalasova Ilona、Shao Zhengping、Zha Shan、Sasanuma Hiroyuki、Hanzlikova Hana、Takeda Shunichi、Caldecott Keith W.
    • Journal Title

      Molecular Cell

      Volume: 81 Issue: 14 Pages: 3018-3030

    • DOI

      10.1016/j.molcel.2021.05.009

    • NAID

      120007052730

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Division of labor of Y-family polymerases in translesion-DNA synthesis for distinct types of DNA damage2021

    • Author(s)
      Y. Inomata, T. Abe, M. Tsuda, S. Takeda, K. Hirota
    • Journal Title

      PLoS One

      Volume: 16

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vertebrate CTF18 and DDX11 essential function in cohesion is bypassed by preventing WAPL-mediated cohesin release2021

    • Author(s)
      R. Kawasumi, T. Abe, I. Psakhye, K. Miyata, K. Hirota, D. Branzei
    • Journal Title

      Genes Dev

      Volume: 35 Pages: 1368-1382

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Reciprocal stabilization of transcription factor binding integrates two signaling pathways to regulate fission yeast fbp1 transcription2021

    • Author(s)
      W. Koda, S. Senmatsu, T. Abe, C.S. Hoffman, K. Hirota
    • Journal Title

      Nucleic Acids Res

      Volume: 49 Issue: 17 Pages: 9809-9820

    • DOI

      10.1093/nar/gkab758

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Follow-up genotoxicity assessment of Ames-positive/equivocal chemicals using the improved thymidine kinase gene mutation assay in DNA repair-deficient human TK6 cells2021

    • Author(s)
      A. Sassa, T. Fukuda, A. Ukai, M. Nakamura, R. Sato, S. Fujiwara, K. Hirota, S. Takeda, K.I. Sugiyama, M. Honma, M. Yasui
    • Journal Title

      Mutagenesis

      Volume: 36 Issue: 5 Pages: 331-338

    • DOI

      10.1093/mutage/geab025

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] lncRNA transcription induces meiotic recombination through chromatin remodelling in fission yeast2021

    • Author(s)
      S. Senmatsu, R. Asada, A. Oda, C.S. Hoffman, K. Ohta, K. Hirota
    • Journal Title

      Commun Biol

      Volume: 4 Pages: 295-295

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 複製ポリメラーゼεの校正活性は断裂した鋳型における安全なフォーク停止に寄与する2022

    • Author(s)
      廣田耕志
    • Organizer
      分子生物学会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 複製ポリメラーゼεの校正活性は断裂した鋳型における安全なフォーク停止に寄与する2022

    • Author(s)
      廣田耕志
    • Organizer
      日本遺伝学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 複製とコヒージョン形成の連動によるゲノム安定性の維持2022

    • Author(s)
      川澄遼太郎 廣田耕志
    • Organizer
      分子生物学会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] トリソミー染色体を標的とした染色体編集2021

    • Author(s)
      阿部 拓也、鈴木 雄也、池谷 鉄兵、廣田 耕志
    • Organizer
      分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Generation of Y chromosome loss cells using HSV-TK-HIS marker genes2021

    • Author(s)
      Mao Ebisawa, Kouji Hirota
    • Organizer
      バイオコンファレンス2021
    • Related Report
      2021 Research-status Report
  • [Presentation] The role of proofreading exonuclease activity of polymeraseε2021

    • Author(s)
      Tomoya Taniguchi,Kouji Hirota
    • Organizer
      バイオコンファレンス2021
    • Related Report
      2021 Research-status Report
  • [Presentation] DNA replication repriming by PrimPol resumes the oncogenic K-Ras induced replication arrest2021

    • Author(s)
      Hayato Saeki, Kouji Hirota
    • Organizer
      バイオコンファレンス2021
    • Related Report
      2021 Research-status Report
  • [Presentation] The assay to evaluate the frequency of aneuploidy2021

    • Author(s)
      Ryo Ishida, Kouji Hirota
    • Organizer
      バイオコンファレンス2021
    • Related Report
      2021 Research-status Report
  • [Presentation] Effect of polymerase ι overexpression on UV sensitivity2021

    • Author(s)
      Minato Watanabe, Kouji Hirota
    • Organizer
      バイオコンファレンス2021
    • Related Report
      2021 Research-status Report
  • [Presentation] Relationship between metabolic-stress-inducsed long noncoding RNA and meiotic recombination2021

    • Author(s)
      Yusuke Tsuruta, Kouji Hirota
    • Organizer
      バイオコンファレンス2021
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2024-01-30  

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