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Structural and functional analysis of chromatin assembly factor CAF-I

Research Project

Project/Area Number 17H06264
Research Category

Grant-in-Aid for Challenging Research (Pioneering)

Allocation TypeSingle-year Grants
Research Field Biomedical structure and function and related fields
Research InstitutionHigh Energy Accelerator Research Organization

Principal Investigator

Senda Toshiya  大学共同利用機関法人高エネルギー加速器研究機構, 物質構造科学研究所, 教授 (30272868)

Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2019: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2018: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2017: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Keywords構造生物学 / クロマチン / 複製 / 複合体 / 遺伝子 / 発現制御 / ゲノム / ゲノム
Outline of Final Research Achievements

A large scale purification system of CAF-I complexes was established and the purified complexes were observed by cryo-EM. The results suggested that the CAF-I complexes disassembled during grid preparation. Subsequently, in order to stabilize the subunit interactions, cross-linking and gel filtration experiments were performed, but the appropriate conditions could not be found. Next, since the dissociation constants of CAF-I and histone H3/H4 are the nanomolar order, the H3/H4 is expected to stabilize CAF-I complex. Then, CAF-I-H3/H4 complexes were purified by gel filtration column. The cryo-EM experiments are in progress, but no clear particle image has been obtained yet.

Academic Significance and Societal Importance of the Research Achievements

本研究計画が対象とするCAF-I複合体は、細胞が獲得した機能を維持する役割を果たす。ということは、CAF-I複合体の機能を阻害することができれば、細胞機能をリセットできる可能性がある。iPS細胞では、転写反応を制御することで細胞機能をリセットし、多能性幹細胞を創出しているが、CAF-I複合体の阻害は複製反応を制御することになる。本研究の目的が達成されれば、これまでとは全く異なる原理によって多能性幹細胞を創出できることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (31 results)

All 2020 2019 2018 2017 Other

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Open Access: 7 results,  Peer Reviewed: 9 results) Presentation (18 results) (of which Int'l Joint Research: 8 results,  Invited: 11 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Crystallographic and cryogenic electron microscopic structures and enzymatic characterization of sulfur oxygenase reductase from Sulfurisphaera tokodaii2020

    • Author(s)
      Yuta Sato, Takashi Yabuki, Naruhiko Adachi, Toshio Moriya, Takatoshi Arakawa, Masato Kawasaki, Chihaya Yamada, Toshiya Senda, Shinya Fushinobu, Takayoshi Wakagi
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2020.05.03.074773

    • Related Report
      2019 Annual Research Report
    • Open Access
  • [Journal Article] An integrated approach to unravel a crucial structural property required for the function of the insect steroidogenic Halloween protein Noppera-bo.2020

    • Author(s)
      Koiwai K, Inaba K, Morohashi K, Enya S, Arai R, Kojima H, Okabe T, Fujikawa Y, Inoue H, Yoshino R, Hirokawa T, Kato K, Fukuzawa K, Shimada-Niwa Y, Nakamura A, Yumoto F, Senda T, Niwa R.
    • Journal Title

      J Biol Chem.

      Volume: - Issue: 20 Pages: 7154-7167

    • DOI

      10.1074/jbc.ra119.011463

    • NAID

      120007165465

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] How Does a Microbial Rhodopsin RxR Realize Its Exceptionally High Thermostability with the Proton-Pumping Function Being Retained?2020

    • Author(s)
      Hayashi Tomohiko、Yasuda Satoshi、Suzuki Kano、Akiyama Tomoki、Kanehara Kanae、Kojima Keiichi、Tanabe Mikio、Kato Ryuichi、Senda Toshiya、Sudo Yuki、Murata Takeshi、Kinoshita Masahiro
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 124 Issue: 6 Pages: 990-1000

    • DOI

      10.1021/acs.jpcb.9b10700

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structures of fukutin-related protein (FKRP), a ribitol-phosphate transferase related to muscular dystrophy.2020

    • Author(s)
      Kuwabara N, Imae R, Manya H, Tanaka T, Mizuno M, Tsumoto H, Kanagawa M, Kobayashi K, Toda T, Senda T, Endo T, Kato R.
    • Journal Title

      Nat Commun.

      Volume: 11 Issue: 1 Pages: 303-303

    • DOI

      10.1038/s41467-019-14220-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit.2018

    • Author(s)
      Ray-Gallet D, Ricketts MD, Sato Y, Gupta K, Boyarchuk E, Senda T, Marmorstein R, Almouzni G.
    • Journal Title

      Nat Commun.

      Volume: 9(1) Issue: 1 Pages: 3103-3103

    • DOI

      10.1038/s41467-018-05581-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural and computational bases for dramatic skeletal rearrangement in anditomin biosynthesis2018

    • Author(s)
      Nakashima, Y., Mitsuhashi, T., Matsuda, Y., Senda, M., Sato, H., Yamazaki, M., Uchiyama, M., Senda, T. & Abe, I.
    • Journal Title

      JACS

      Volume: 140 Issue: 30 Pages: 9743-9750

    • DOI

      10.1021/jacs.8b06084

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of the nitrosuccinate lyase CreD in complex with fumarate provides insights into the catalytic mechanism for nitrous acid elimination.2018

    • Author(s)
      Katsuyama Y, Sato Y, Sugai Y, Higashiyama Y, Senda M, Senda T, Ohnishi Y.
    • Journal Title

      FEBS J.

      Volume: 285(8) Issue: 8 Pages: 1540-1555

    • DOI

      10.1111/febs.14429

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of the DNA-binding domain of the LysR-type transcriptional regulator CbnR in complex with a DNA fragment of the recognition-binding site in the promoter region.2018

    • Author(s)
      Koentjoro MP, Adachi N, Senda M, Ogawa N, Senda T.
    • Journal Title

      FEBS J.

      Volume: 285(5) Issue: 5 Pages: 977-989

    • DOI

      10.1111/febs.14380

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure function and engineering of multifunctional non-heme iron dependent oxygenases in fungal meroterpenoid biosynthesis2018

    • Author(s)
      Nakashima Yu、Mori Takahiro、Nakamura Hitomi、Awakawa Takayoshi、Hoshino Shotaro、Senda Miki、Senda Toshiya、Abe Ikuro
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41467-017-02371-w

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Leading role of TBP in the Establishment of Complexity in Eukaryotic Transcription Initiation Systems2017

    • Author(s)
      Kawakami Eiryo、Adachi Naruhiko、Senda Toshiya、Horikoshi Masami
    • Journal Title

      Cell Reports

      Volume: 21 Issue: 13 Pages: 3941-3956

    • DOI

      10.1016/j.celrep.2017.12.034

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] クライオ電子顕微鏡:気になっていること・困っていること@KEK2019

    • Author(s)
      安達成彦
    • Organizer
      日本顕微鏡学会・第75回学術講演会(口頭発表)(招待講演)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Structure analysis of transcription related complexes and installation of cryo-EM in KEK2019

    • Author(s)
      安達成彦
    • Organizer
      第19回日本蛋白質科学会年会・第71回日本細胞生物学会大会 合同年次大会(口頭発表)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] クライオ電子顕微鏡で生体分子の形を明らかにする2019

    • Author(s)
      安達成彦
    • Organizer
      KEK公開講座「生物学におけるクライオ電子顕微鏡」(口頭発表)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Structure analysis of transcription related complexes and installation of cryo-EM in KEK2019

    • Author(s)
      Naruhiko Adachi, Masato Kawasaki, Toshio Moriya, Fumiaki Yumoto, Kotaro Koiwai, Akira Shinoda, Yusuke Yamada, Toshiya Senda
    • Organizer
      The 2019 American Crystallographic Association Annual Meeting(ポスター発表)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 単粒子解析の原理と実際:KEKにおける共同利用型クライオ電子顕微鏡の立ち上げを例として2019

    • Author(s)
      安達成彦
    • Organizer
      日本プロテオーム学会2019年大会・第70回日本電気泳動学会総会(口頭発表)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Structure analysis of transcription related complexes and installation of cryo-EM in KEK2019

    • Author(s)
      Naruhiko Adachi, Masato Kawasaki, Toshio Moriya, Fumiaki Yumoto, Kotaro Koiwai, Akira Shinoda, Yusuke Yamada, Toshiya Senda
    • Organizer
      Cold Spring Harbor Laboratory meeting, Mechanisms of eukaryotic transcription(ポスター発表)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] KEKクライオ電顕の現状2019

    • Author(s)
      千田俊哉・安達成彦・川崎政人・守屋俊夫・山田悠介・篠田晃・小祝孝太郎
    • Organizer
      生理研研究会「クライオ電子顕微鏡によるタンパク質の高分解能単粒子構造解析」
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] KEKにおけるクライオ電顕施設の紹介2019

    • Author(s)
      千田俊哉・安達成彦・川崎政人・守屋俊夫・山田悠介・篠田晃・小祝孝太郎
    • Organizer
      第42回日本分子生物学会年会(口頭発表)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] マルチサブユニット複合体の研究とKEKクライオ電子顕微鏡の現状2019

    • Author(s)
      安達成彦, 千田俊哉
    • Organizer
      蛋白研セミナー(第1回構造生命科学研究会)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Structural Biology Research Center.2018

    • Author(s)
      千田俊哉
    • Organizer
      千葉大-KEK第1回合同シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Study of GTP sensor -importance of interdisiuplinary collaboration.2018

    • Author(s)
      千田俊哉
    • Organizer
      International Symposium of Quantum Beam Science
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 創薬等先端技術支援基盤プラットフォームにおけるクライオ 電子顕微鏡のネットワーク化と利用について2018

    • Author(s)
      千田俊哉
    • Organizer
      Study of GTP sensor importance of interdisiuplinary collaboration
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒストンシャペロンHIRA の構造機能相関2018

    • Author(s)
      佐藤優花里、千田俊哉
    • Organizer
      第18回日本蛋白質科学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Leading role of TBP in the establishment of complexity in eukaryotic transcription initiation systems.2018

    • Author(s)
      Naruhiko Adachi, Eiryo Kawakami, Toshiya Senda, Masami Horikoshi
    • Organizer
      The 18th Annual meeting of PSSJ
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Structure-based integrated approach for analysis of the GTP metabolism.2018

    • Author(s)
      Toshiya Senda
    • Organizer
      American Crystallographic Association (ACA) 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Leading role of TBP in the establishment of complexity in eukaryotic transcription initiation systems2018

    • Author(s)
      Naruhiko Adachi, Eiryo Kawakami, Toshiya Senda, Masami Horikoshi
    • Organizer
      Cold Spring Harbor Laboratory Meeting: Epigenetics & Chromatin
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] KEKクライオ電顕の立ち上げと単粒子解析2018

    • Author(s)
      安達成彦, 川崎政人, 小祝孝太郎, 湯本史明, 守屋俊夫, 篠田晃, 山田悠介, 千田俊哉
    • Organizer
      生理研研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Improved method for soluble expression and rapid purification of yeast TFIIA2017

    • Author(s)
      Naruhiko Adachi, Kyohei Aizawa, Yuka Kratzer, Shinya Saijo, Nobutaka Shimizu, Toshiya Senda
    • Organizer
      Cold Spring Harbor Lab meeting, MECHANISMS OF EUKARYOTIC TRANSCRIPTION
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Book] 実験医学増刊・イメージング時代の構造生命科学2020

    • Author(s)
      安達成彦、千田俊哉
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2019 Annual Research Report
  • [Remarks] 高エネルギー加速器研究機構・物質構造科学研究所・構造生物学研究センター

    • URL

      https://www2.kek.jp/imss/sbrc/

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Remarks] 高エネルギー加速器研究機構・物質構造科学研究所・構造生物学研究センター

    • URL

      http://www2.kek.jp/imss/sbrc/

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-07-21   Modified: 2021-02-19  

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