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Comprehensive understanding of H3K9me-mediated transcriptional silencing

Research Project

Project/Area Number 18H03991
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Shinkai Yoichi  国立研究開発法人理化学研究所, 開拓研究本部, 主任研究員 (20211972)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥44,070,000 (Direct Cost: ¥33,900,000、Indirect Cost: ¥10,170,000)
Fiscal Year 2021: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2020: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2019: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2018: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Keywordsepigenetics / エピジェネティクス / 転写抑制 / ヒストンメチル化 / DNAメチル化 / CRISPR/CAS9
Outline of Final Research Achievements

The various tissues/organs that make up our body consist of distinct types of cells. The nature of this different cell type is determined by the expression of different sets of genes. Which gene is turned ON or OFF in cells with different properties is regulated by the control of genome and acquired epigenome information. Epigenome information in the OFF state includes methylation of histone H3 lysine 9 residue (H3K9). In this study, we comprehensively analyzed what factors contribute to the control of the OFF state downstream of H3K9 methylation. As a result, we identified a number of novel factors in addition to the previously known factors. Currently, we are elucidating the role of these novel factors. Through this research, we would like to contribute to the development of a method to arbitrarily turn genes on and off.

Academic Significance and Societal Importance of the Research Achievements

遺伝子のスイッチオン・オフのパターンが細胞種ごとに違うことで、異なる性質を持つ細胞を作ることが出来る。スイッチオフでは遺伝子が発現しないような仕組みが様々に働いている。その中心をなす機構として、ヒストンという蛋白質に施される様々な化学修飾による制御がある。ヒストンH3の9番目のリシン(H3K9)のメチル化は、スイッチオフに寄与する。今回の研究では、H3K9メチル化の下流でどのような因子がスイッチオフに作用するか、その機構の一端を明らかにした。様々な疾患では、スイッチのオン・オフ制御が不全になっている。今回の研究は、疾患をスイッチ制御の観点から理解することに貢献する研究である。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (47 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (16 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 16 results,  Open Access: 16 results) Presentation (25 results) (of which Int'l Joint Research: 3 results,  Invited: 9 results) Remarks (5 results)

  • [Int'l Joint Research] Radboud University Medical Center(オランダ)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Mammalian HEMK1 methylates glutamine residue of the GGQ motif of mitochondrial release factors2022

    • Author(s)
      Fang Qi、Kimura Yusuke、Shimazu Tadahiro、Suzuki Takehiro、Yamada Ayumi、Dohmae Naoshi、Iwasaki Shintaro、Shinkai Yoichi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 4104-4104

    • DOI

      10.1038/s41598-022-08061-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells2022

    • Author(s)
      Fukuda Kei、Makino Yoshinori、Kaneko Satoru、Shimura Chikako、Okada Yuki、Ichiyanagi Kenji、Shinkai Yoichi
    • Journal Title

      eLife

      Volume: 11

    • DOI

      10.7554/elife.76822

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of mammalian 3D genome organization and histone H3K9 dimethylation by H3K9 methyltransferases2021

    • Author(s)
      Fukuda Kei、Shimura Chikako、Miura Hisashi、Tanigawa Akie、Suzuki Takehiro、Dohmae Naoshi、Hiratani Ichiro、Shinkai Yoichi
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 571-571

    • DOI

      10.1038/s42003-021-02089-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A cost efficient protocol to introduce epitope tags by CRISPR-Cas9 mediated gene knock-in with asymmetric semi-double stranded template2021

    • Author(s)
      Fang Qi、Shinkai Yoichi
    • Journal Title

      MethodsX

      Volume: 8 Pages: 101365-101365

    • DOI

      10.1016/j.mex.2021.101365

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Derepression of inflammation-related genes link to microglia activation and neural maturation defect in a mouse model of Kleefstra syndrome2021

    • Author(s)
      Yamada Ayumi、Hirasawa Takae、Nishimura Kayako、Shimura Chikako、Kogo Naomi、Fukuda Kei、Kato Madoka、Yokomori Masaki、Hayashi Tetsutaro、Umeda Mana、Yoshimura Mika、Iwakura Yoichiro、Nikaido Itoshi、Itohara Shigeyoshi、Shinkai Yoichi
    • Journal Title

      iScience

      Volume: 24 Issue: 7 Pages: 102741-102741

    • DOI

      10.1016/j.isci.2021.102741

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DMRT1-mediated reprogramming drives development of cancer resembling human germ cell tumors with features of totipotency2021

    • Author(s)
      Taguchi Jumpei、Shibata Hirofumi、Kabata Mio、Kato Masaki、Fukuda Kei、Tanaka Akito、Ohta Sho、Ukai Tomoyo、Mitsunaga Kanae、Yamada Yosuke、Nagaoka So I、Yamazawa Sho、Ohnishi Kotaro、Woltjen Knut、Ushiku Tetsuo、Ozawa Manabu、Saitou Mitinori、Shinkai Yoichi、Yamamoto Takuya、Yamada Yasuhiro
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 5041-5041

    • DOI

      10.1038/s41467-021-25249-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A loss-of-function variant in SUV39H2 identified in autism-spectrum disorder causes altered H3K9 trimethylation and dysregulation of protocadherin β-cluster genes in the developing brain2021

    • Author(s)
      Balan Shabeesh、-25名-, Shinkai Yoichi、Yoshikawa Takeo
    • Journal Title

      Molecular Psychiatry

      Volume: 26 Issue: 12 Pages: 7550-7559

    • DOI

      10.1038/s41380-021-01199-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Propargylic Se-adenosyl-l-selenomethionine: A Chemical Tool for Methylome Analysis2021

    • Author(s)
      Sohtome Yoshihiro、Shimazu Tadahiro、Shinkai Yoichi、Sodeoka Mikiko
    • Journal Title

      Accounts of Chemical Research

      Volume: 54 Issue: 20 Pages: 3818-3827

    • DOI

      10.1021/acs.accounts.1c00395

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SETDB1-Mediated Silencing of Retroelements2020

    • Author(s)
      Fukuda Kei、Shinkai Yoichi
    • Journal Title

      Viruses

      Volume: 12 Issue: 6 Pages: 596-596

    • DOI

      10.3390/v12060596

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The fibronectin type-III (FNIII) domain of ATF7IP contributes to efficient transcriptional silencing mediated by the SETDB1 complex2020

    • Author(s)
      Tsusaka Takeshi、Fukuda Kei、Shimura Chikako、Kato Masaki、Shinkai Yoichi
    • Journal Title

      Epigenetics & Chromatin

      Volume: 13 Issue: 1 Pages: 52-52

    • DOI

      10.1186/s13072-020-00374-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ATF7IP regulates SETDB1 nuclear localization and increases its ubiquitination2019

    • Author(s)
      Tsusaka T. Shimura C. *Shinkai Y.
    • Journal Title

      EMBO reports

      Volume: 20 Issue: 12

    • DOI

      10.15252/embr.201948297

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure of the UHRF1 Tandem Tudor Domain Bound to a Methylated Non-histone Protein, LIG1, Reveals Rules for Binding and Regulation2019

    • Author(s)
      Kori, S. Ferry, L. Matano, S. Jimenji, T. Kodera, N. Tsusaka, T. Matsumura, R. Oda, T. Sato, M. Dohmae, N. Ando, T. Shinkai, Y. Defossez, P. A. Arita, K.
    • Journal Title

      Structure

      Volume: 27 Issue: 3 Pages: 1-12

    • DOI

      10.1016/j.str.2018.11.012

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Histone H3K9 Methyltransferase G9a in Oocytes Is Essential for Preimplantation Development but Dispensable for CG Methylation Protection.2019

    • Author(s)
      Yeung WKA, Brind’Amour J, Hatano Y, Yamagata K, Feil R, Matthew C. Lorincz MC, Tachibana M, Shinkai Y, Sasaki H*.
    • Journal Title

      Cell Rep.

      Volume: 27 Issue: 1 Pages: 282-293

    • DOI

      10.1016/j.celrep.2019.03.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A CRISPR knockout screen Identifies SETDB1-target retroelement silencing factors in embryonic stem cells2018

    • Author(s)
      Fukuda Kei、Okuda Akihiko、Yusa Kosuke、Shinkai Yoichi
    • Journal Title

      Genome Research

      Volume: 28 Issue: 6 Pages: 1-13

    • DOI

      10.1101/gr.227280.117

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tri-methylation of ATF7IP by G9a/GLP recruits the chromodomain protein MPP8.2018

    • Author(s)
      Tsusaka T, Kikuchi M, Shimazu T, Suzuki T, Sohtome Y, Akakabe M, Sodeoka M, Dohmae N, Takashi Umehara T, Shinkai Y*.
    • Journal Title

      Epigenetics and chromatin.

      Volume: 11 Issue: 1 Pages: 56-56

    • DOI

      10.1186/s13072-018-0231-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] G9a-dependent histone methylation can be induced in G1 phase of cell cycle.2018

    • Author(s)
      Fukuda M, Sakaue-Sawano A, Shimura C, Tachibana M, Miyawaki A, Shinkai Y.
    • Journal Title

      Sci. Rep.

      Volume: 9 Issue: 1 Pages: 956-956

    • DOI

      10.1038/s41598-018-37507-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] H3K9 and H3K27 methylation pathways exclusively and coordinately regulate heterochromatin organization2022

    • Author(s)
      Yoichi Shinkai
    • Organizer
      The 30th Hot Spring Harbor International Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Coordinate regulation of heterochromatin organization by H3K9 and H3K27 methylation pathways2022

    • Author(s)
      Yoichi Shinkai
    • Organizer
      2022 International Symposium of the Epigenome Dynamics Control Research Center
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Discovery of novel protein histidine pi-methyltransferase2021

    • Author(s)
      Yoichi Shinkai
    • Organizer
      Pacifichem 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 反復配列に引き起こされる哺乳類異所的 高次クロマチン形成系の構築と解析2021

    • Author(s)
      白井温子、眞貝洋一
    • Organizer
      トランスポゾン研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Reversibility of neurological phenotypes in Kleefstra syndrome model mouse by post-natal GLP supply2021

    • Author(s)
      Yamada A. Hirasawa T. Nishimura K. Shimura C. Kogo N. Fukuda K. Kato M. Yokomori M. Hayashi T. Umeda M. Yoshimura M. Iwakura Y. Nikaido I. Itohara S. Shinkai Y
    • Organizer
      日本人類遺伝学会第66回大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] METTL18-mediated histidine methylation on ribosome protein modulates tyrosine translation for proteostasis maintenance2021

    • Author(s)
      Matsuura-Suzuki E. Shimazu T. Takahashi M. Dohmae N. Ito T. Shinkai Y. Iwasaki S
    • Organizer
      第22回日本RNA学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 抑制性クロマチン修飾による核内高次クロマチン構造制御2021

    • Author(s)
      福田渓、志見剛、志村知古、木村宏、眞貝洋一
    • Organizer
      第39回 染色体ワークショップ・第19回 核ダイナミクス研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] METTL18-mediated histidine methylation on ribosome protein modulates tyrosine translation for proteostasis maintenance2021

    • Author(s)
      Matsuura-Suzuki E. Shimazu T. Takahashi M. Dohmae N. Ito T. Shinkai Y. Iwasaki S
    • Organizer
      RNA2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] 自発運動によるクリーフストラ症候群脳神経症状の改善効果2021

    • Author(s)
      山田亜夕美、西村佳也子、眞貝洋一
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] マウス細胞における異所的へテロクロマチン形成系の構築2021

    • Author(s)
      宮野可菜, 白井温子, 眞貝洋一, 大関淳一郎, 舛本寛, 中山学, 阿部訓也, 鈴木伸之介
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 反復配列に引き起こされる哺乳類異所的高次クロマチン形成系の構築と解析2021

    • Author(s)
      白井温子、大関淳一、舛本寛、中山学、眞貝洋一
    • Organizer
      第38回染色体WS・第19回核ダイナミクス研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Between H3K9 and DNA methylations-the crosstalk in two main gene silencing pathways2021

    • Author(s)
      Fang Qi
    • Organizer
      第14回日本エピジェネティクス研究会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] H3K9メチル化を介した遺伝子発現抑制機構の解明2021

    • Author(s)
      清水泰希、沖昌也、眞貝洋一
    • Organizer
      第14回日本エピジェネティクス研究会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 反復配列に引き起こされる哺乳類異所的高次クロマチン形成系の構築と解析2021

    • Author(s)
      白井温子、大関淳一、舛本寛、中山学、眞貝洋一
    • Organizer
      第14回日本エピジェネティクス研究会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Compartment-dependent regulation of heterochromatin formation in mouse embryonic stem cells2021

    • Author(s)
      福田渓、三浦尚、谷川明恵、平谷伊智朗、眞貝洋一
    • Organizer
      第14回日本エピジェネティクス研究会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] エピゲノムによる転写抑制機構の解明2019

    • Author(s)
      眞貝洋一
    • Organizer
      第37回染色体ワークショップ・第18回核ダイナミクス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] エピゲノム操作による生命機能への介入の可能性2019

    • Author(s)
      眞貝洋一
    • Organizer
      第112回日本繁殖生物学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 反復配列に引き起こされる哺乳類異所的高次クロマチン形成2019

    • Author(s)
      白井温子、大関淳一郎、舛本寛、中山学、眞貝洋一
    • Organizer
      第13回日本エピジェネティクス研究会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Setdb1-Atf7ip 複合体による転写抑制機構2019

    • Author(s)
      眞貝洋一
    • Organizer
      研究会「染色体研究の最前線2019」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] H3K9メチル化酵素によるレトロウイルス転写抑制の分子機構2018

    • Author(s)
      眞貝洋一
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] エピゲノムの確立・維持と可変・可塑性のダイナミクス2018

    • Author(s)
      眞貝洋一
    • Organizer
      日本生化学会北陸支部第36回大会シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 内在性レトロウイルスの活性化機構と自然免疫反応2018

    • Author(s)
      竹本 経緯子、加藤 雅紀、眞貝 洋一
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Kleefstra症候群の後天的エピゲノム改変による治療可能性の探求と発症機構の解明2018

    • Author(s)
      山田亜夕美、西村佳也子、志村知古、平澤孝枝、眞貝洋一
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] G9aは細胞周期のどのタイミングでヒストンH3K9をメチル化できるのか?2018

    • Author(s)
      福田 幹子、阪上-沢野 朝子、宮脇 敦史、志村 知古、立花 誠、眞貝 洋一
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Kleefstra症候群モデルマウスの自閉症様表現型は後天的エピゲノム改変により回復できるか-そのタイミングと効果-2018

    • Author(s)
      横森 将輝、加藤 まどか、山田 亜夕美、西村 佳也子、眞貝 洋一、平澤 孝枝
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Remarks] エピゲノム異常に起因する脳機能不全の治療の可能性-クリーフストラ症候群の治療法開発に前進-

    • URL

      https://www.riken.jp/press/2021/20210706_2/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] ヒストンメチル化による自閉症の新しいメカニズムを発見-自閉スペクトラム症の治療薬開発に役立つ可能性-

    • URL

      https://www.riken.jp/press/2021/20210715_2/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] A genetic brain disease reversed after birth

    • URL

      https://www.riken.jp/en/news_pubs/research_news/pr/2021/20210706_2/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 精子のエピゲノムは人それぞれ-生殖細胞におけるレトロエレメントの不完全制御-

    • URL

      https://www.riken.jp/press/2022/20220413_2/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] Research News

    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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