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Experimental approaches testing cis-regulatory element driven evolutionary mechanisms by genome editing tools.

Research Project

Project/Area Number 15H04408
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Evolutionary biology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Sumiyama Kenta  国立研究開発法人理化学研究所, 生命機能科学研究センター, ユニットリーダー (00370114)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywordsシス因子 / 進化 / ゲノム編集 / Dlx遺伝子 / エンハンサー / 発現制御 / 発生分化 / 発生・分化
Outline of Final Research Achievements

We experimentally verified whether it is possible to artificially acquire cis-elements in the distal region of the genomic endogenous toolkit gene and cause gene expression evolution. When ectopic enhancer knock-in mice were generated using the Dlx3/4 gene cluster as a model system, Dlx3/4 gene expression was upregulated by the inserted enhancer. This result indicated that target gene expression change could be realized by knocking in the ectopic enhancer at appropriate genomic position. In addition, we have established an efficient genome editing protocol for knock-in.

Academic Significance and Societal Importance of the Research Achievements

これまで有力な仮説とされてきたシス因子の新規獲得による遺伝子発現量変化の進化が実際に容易に可能であることを、適切な位置でのエンハンサーノックイン実験を行うことで示すことができた。制御配列により進化が駆動しうることが示されたことで、進化メカニズムの理解が進む事が期待できる。また進化の理解だけで無く、その原理を応用することで新しい有用生物作製の方法論へ発展することも期待され、新規技術開発のシードとなる可能性がある。

Report

(4 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (22 results)

All 2019 2018 2017 2016 2015 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (16 results) (of which Invited: 5 results) Remarks (1 results)

  • [Journal Article] Expression of plasma membrane calcium ATPases confers Ca2+/H+ exchange in rodent synaptic vesicles2019

    • Author(s)
      Ono Yoshiyasu、Mori Yasunori、Egashira Yoshihiro、Sumiyama Kenta、Takamori Shigeo
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1-17

    • DOI

      10.1038/s41598-019-40557-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Easy and efficient production of completely embryonic-stem-cell-derived mice using a micro-aggregation device2018

    • Author(s)
      Sumiyama Kenta、Matsumoto Naomi、Gar?on-Yoshida Junko、Ukai Hideki、Ueda Hiroki R.、Tanaka Yo
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 9 Pages: e0203056-e0203056

    • DOI

      10.1371/journal.pone.0203056

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Muscarinic Acetylcholine Receptors Chrm1 and Chrm3 Are Essential for REM Sleep2018

    • Author(s)
      Niwa Yasutaka、Kanda Genki N.、Yamada Rikuhiro G.、Shi Shoi、Sunagawa Genshiro A.、Ukai-Tadenuma Maki、Fujishima Hiroshi、Matsumoto Naomi、Masumoto Koh-hei、Nagano Mamoru、Kasukawa Takeya、Galloway James、Perrin Dimitri、Shigeyoshi Yasufumi、Ukai Hideki、Kiyonari Hiroshi、Sumiyama Kenta、Ueda Hiroki R.
    • Journal Title

      Cell Reports

      Volume: 24 Issue: 9 Pages: 2231-2247.e7

    • DOI

      10.1016/j.celrep.2018.07.082

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition.2017

    • Author(s)
      Fumoto, K., Takigawa-Imamura, H., Sumiyama, K., Kaneiwa, T., and Kikuchi, A.
    • Journal Title

      Development

      Volume: 144 Pages: 151-162

    • DOI

      10.1242/dev.141325

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Intravital Forster resonance energy transfer imaging reveals osteopontin‐mediated polymorphonuclear leukocyte activation by tumor cell emboli2017

    • Author(s)
      Yuji Kamioka, Kanako Takakura, Kenta Sumiyama, Michiyuki Matsuda
    • Journal Title

      Cancer Science

      Volume: 108(2) Issue: 2 Pages: 226-235

    • DOI

      10.1111/cas.13132

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Triple-target CRISPR enabled almost perfect whole-body bi-allelic knockouts at first generation2018

    • Author(s)
      Kenta Sumiyama
    • Organizer
      Genome Editing Towards Medicinal Applications, 第9回武田科学振興財団薬科学シンポジウム, 武田薬品研修所, 吹田市
    • Related Report
      2017 Annual Research Report
  • [Presentation] 初代マウスで表現型解析可能なゲノム編集技術の開発と進化学研究への応用2018

    • Author(s)
      隅山 健太
    • Organizer
      第5回ケモビ研究会, KKRホテル熱海
    • Related Report
      2017 Annual Research Report
  • [Presentation] Inferring ancestral state before WGD from enhancers and CTCF/cohesin loops in developmental genes.2018

    • Author(s)
      Kenta Sumiyama
    • Organizer
      SMBE 2018 at Yokohama: 50th anniversary of the neutral theory of molecular evolution, パシフィコ横浜
    • Related Report
      2017 Annual Research Report
  • [Presentation] ゲノム重複前の脊椎動物表現型を推定する新しい試み2018

    • Author(s)
      隅山 健太
    • Organizer
      シンポジウムS5:Basal lineage は「原始的」か?~生物界と分野を超えて 日本進化学会第20回大会, 東京大学駒場Ⅰキャンパス, 東京
    • Related Report
      2017 Annual Research Report
  • [Presentation] Genome editing for synthetic biology2017

    • Author(s)
      Kenta Sumiyama
    • Organizer
      Scientific meeting <Evolutionary Genomics: Themes and Variations>, National Institute of Genetics, Mishima
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] トリプル CRISPR 法による第一世代での両アリル完全ノックアウトマウス作製2017

    • Author(s)
      隅山 健太、砂川 玄志郎、鵜飼(蓼沼)磨貴、ディミトリー ぺリン、上田 泰己
    • Organizer
      第64回日本実験動物学会総会、ビッグパレットふくしま、郡山市
    • Related Report
      2017 Annual Research Report
  • [Presentation] トリプル CRISPR 法による第一世代での両アリル完全ノックアウトマウス作製2017

    • Author(s)
      隅山 健太
    • Organizer
      第30回モロシヌス研究会、ホテルグリーンピア南阿蘇、熊本県南阿蘇村
    • Related Report
      2017 Annual Research Report
  • [Presentation] トリプル CRISPR 法による第一世代での両アリル完全ノックアウトマウス作製2017

    • Author(s)
      隅山 健太
    • Organizer
      日本ゲノム編集学会第2回大会、千里ライフサイエンスセンター、大阪府豊中市
    • Related Report
      2017 Annual Research Report
  • [Presentation] Dlx4遺伝子の進化学的解析とゲノム編集による実験検証2017

    • Author(s)
      隅山 健太
    • Organizer
      日本進化学会第19回大会、京都大学吉田キャンパス、京都市
    • Related Report
      2017 Annual Research Report
  • [Presentation] 遺伝子改変マウスを用いた非コード領域の進化的研究2017

    • Author(s)
      隅山 健太
    • Organizer
      日本遺伝学会第89回大会、岡山大学津島キャンパス、岡山市
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Triple-target CRISPR enabled almost perfect whole-body bi-allelic knockouts at first generation2016

    • Author(s)
      Kenta Sumiyama
    • Organizer
      JSDB Special Symposium: Frontier of Developmental Biology Hosted by JSDB
    • Related Report
      2016 Annual Research Report
  • [Presentation] トリプルCRISPR 法による第一世代での両アリル完全ノックアウトマウス作製2016

    • Author(s)
      隅山 健太,砂川 玄志郎,鵜飼(蓼沼) 磨貴,ディミトリー ペリン,上田 泰己
    • Organizer
      第68回日本細胞生物学会大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] トリプルCRISPR 法による第一世代での両アリル完全ノックアウトマウス作製2016

    • Author(s)
      隅山 健太,砂川 玄志郎,鵜飼(蓼沼) 磨貴,ディミトリー ペリン,上田 泰己
    • Organizer
      第6回 Tokyo Vertebrate Morphology Meeting
    • Related Report
      2016 Annual Research Report
  • [Presentation] トリプルCRISPR 法による第一世代での両アリル完全ノックアウトマウス作製2016

    • Author(s)
      隅山 健太,砂川 玄志郎,鵜飼(蓼沼) 磨貴,ディミトリー ペリン,上田 泰己
    • Organizer
      日本遺伝学会第88回大会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 哺乳類Dlx遺伝子クラスターにおけるシス制御因子の機能解析と進化2016

    • Author(s)
      隅山 健太
    • Organizer
      第39回日本分子生物学会年会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Genome editing technologies for gene knockout phenotyping on founder mice2015

    • Author(s)
      Kenta Sumiyama
    • Organizer
      合成生物学の現在と未来 The present and the future of synthetic biology, RIKEN Symposium
    • Place of Presentation
      RIKEN KOBE CDB, 兵庫県神戸市
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Remarks] 高速ゲノム変異マウス作製支援ユニット・独自の発生工学技術を開発し、ゲノム機能発現・進化の謎に迫る

    • URL

      http://www.bdr.riken.jp/jp/research/labs/sumiyama-k/index.html

    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2020-03-30  

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