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Integrated elucidation of the transcriptional regulatory mechanisms of human ABO blood group gene using iPS cells

Research Project

Project/Area Number 26293161
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Legal medicine
Research InstitutionGunma University

Principal Investigator

Kominato Yosihhiko  群馬大学, 医学(系)研究科(研究院), 教授 (30205512)

Co-Investigator(Kenkyū-buntansha) 高橋 遥一郎  群馬大学, 医学(系)研究科(研究院), 助教 (50640538)
佐野 利恵  群馬大学, 医学(系)研究科(研究院), 講師 (70455955)
中島 たみ子  群馬大学, 医学(系)研究科(研究院), 講師 (40008561)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2014: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
KeywordsABO式血液型 / 転写調節 / エンハンサー / 法医学 / ABO式血液型遺伝子 / ABO遺伝子
Outline of Final Research Achievements

The human ABO blood group system is important in blood transfusion. However, the mechanisms regulating ABO gene expression remain obscure in epithelial cells. On the basis of DNase I-hypersensitive sites and histone modifications in and around ABO in epithelial cells, we prepared reporter plasmids including a putative enhancer downstream from ABO. Subsequent luciferase assays indicated a novel positive regulatory element (+22.6-kb site) in an epithelial cell-specific manner. Expression of ABO and B-antigen was reduced in gastric cancer KATOIII cells by biallelic deletion of the site using the CRISPR/Cas9 system. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that the site bound to an epithelial cell-specific transcription factor Elf5. ELF5 knockdown with shRNA reduced both endogenous transcription from ABO and B-antigen expression in the cells. ABO expression seems to be dependent upon an enhancer bound by Elf5 in epithelial cells.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(11 results)

All 2016 2015 2014

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 7 results,  Open Access: 5 results) Presentation (4 results)

  • [Journal Article] Epithelial expression of human ABO blood group gene is dependent upon a downstream regulatory element functioning through an epithelial cell-specific transcription factor, Elf5.2016

    • Author(s)
      Sano R, Nakajima T, Takahashi Y, Kubo R, Kobayashi M, Takahashi K, Takeshita H, Ogasawara K, Kominato Y.
    • Journal Title

      J Genet.

      Volume: 291 Pages: 189-192

    • DOI

      10.1074/jbc.m116.730655

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] BO alleles are linked with haplotypes of an erythroid cell-specific regulatory element in intron 1 with a few exceptions attributable to genetic recombination.2016

    • Author(s)
      Nakajima T, Sano R, Takahashi Y, Watanabe K, Kubo R, Kobayashi M, Takahashi K, Takeshita H, Kominato Y.
    • Journal Title

      Vox Sanguinis

      Volume: 11 Pages: 90-92

    • DOI

      10.1111/vox.12312

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Presence of nucleotide substitutions in the ABO promoter in individuals with phenotypes A3 and B3.2016

    • Author(s)
      Isa K, Yamamuro Y, Ogasawara K, Yabe R, Ogiyama Y, Ito S, Takahashi Y, Y Kominato Y, Sano R, Uchikawa M.
    • Journal Title

      Vox Sanguinis

      Volume: 110 Pages: 285-287

    • DOI

      10.1111/vox.12363

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A 3.0-kb delation including an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene in an individual with the Bm phenotype2015

    • Author(s)
      Sano R, Kuboya E, Nakajima T, Takahashi Y, Takahashi K, Kubo R, Kominato Y, Takeshita H, Yamao H, Kishida T, Isa K, Ogasawara K, Uchikawa M
    • Journal Title

      Vox Sanguinis

      Volume: 108 Pages: 310-313

    • DOI

      10.1111/vox.12216

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Blood group gene is barely expressed in vitro erythroid culture of Bm-derived CD34+ cells without an erythroid cell-specific regulatory element2015

    • Author(s)
      Sano R, Nogawa T, Nakajima T, Takahashi Y, Kubo R, Kominato Y, Yokohama A, Tsukada J, Yamao H, Kishida T, Ogasawara K, Uchikawa M
    • Journal Title

      Vox Sanguinis

      Volume: 108 Pages: 302-309

    • DOI

      10.1111/vox.12220

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Presence of nucleotide substitutions in transcriptional regulatory elements such as the erythroid cell-specific enhancer-like element and the ABO promoter in individuals with phenotypes A3 and B3, respectively.2014

    • Author(s)
      Takahashi Y, Isa K, Sano R, Nakajima T, Kubo R, Takahashi K, Kominato Y, Michino J, Masuno A, Tsuneyama H, Ito S, Ogasawara K, Uchikawa M
    • Journal Title

      Vox Sang

      Volume: 107 Pages: 171-180

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Deletion of the RUNX1 binding site in the erythroid cell-specific regulatory element of the ABO gene in two individuals with the Am phenotype.2014

    • Author(s)
      Takahashi Y, Isa K, Sano R, Nakajima T, Kubo R, Takahashi K, Kominato Y, Tsuneyama H, Ogasawara K, Uchikawa M
    • Journal Title

      Vox Sanguinis

      Volume: 106 Pages: 167-175

    • DOI

      10.1111/vox.12077

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ABO遺伝子の発現量変動の機序解明と、薬剤刺激による血液型抗原量の制御.2016

    • Author(s)
      高橋遥一郎, 佐野利恵, 高橋圭子, 窪理英子, 中島たみ子, 小湊慶彦.
    • Organizer
      第100次日本法医学会学術全国集会
    • Place of Presentation
      東京
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] ABO式血液型遺伝子エンハンサーのハプロタイプはABO遺伝子型とリンクしている.2016

    • Author(s)
      中島たみ子, 佐野利恵, 高橋遥一郎, 竹下治男, 安田年博, 小湊慶彦.
    • Organizer
      第100次日本法医学会学術全国集会.
    • Place of Presentation
      東京
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Bm型では赤血球系細胞においてB遺伝子の発現が極めて低下している-CD34陽性細胞を用いた赤血球系細胞への分化培養実験-.2015

    • Author(s)
      佐野利恵、中島たみ子、高橋遥一郎、小湊慶彦
    • Organizer
      日本DNA多型学会第24回学術集会
    • Place of Presentation
      岡山県岡山市
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] ABO式血液型遺伝子エンハンサーハプロタイプの型特異性.2015

    • Author(s)
      中島たみ子、佐野利恵、高橋遥一郎、窪 理英子、高橋圭子、小林もも子、渡邊華帆、小湊慶彦、竹下治男、安田年博
    • Organizer
      日本DNA多型学会第24回学術集会
    • Place of Presentation
      岡山県岡山市
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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