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2015 Fiscal Year Annual Research Report

新しいエピゲノムとしてのDNAの2次構造による転写調節

Research Project

Project/Area Number 26670171
Research InstitutionFujita Health University

Principal Investigator

倉橋 浩樹  藤田保健衛生大学, 総合医科学研究所, 教授 (30243215)

Project Period (FY) 2014-04-01 – 2016-03-31
Keywords習慣流産 / エピゲノム / グアニン四重鎖 / アネキシンV / プロモーター / 多型 / 2次構造 / バイサルファイト法
Outline of Annual Research Achievements

DNA2次構造の解析は、ゲノム配列情報に付加的機能を媒介する新しいエピゲノムとして重要である。G-quadruplex (G4)と呼ばれる四重鎖DNAもそのひとつであり、転写、複製、組換えの調節に関係するといわれている。胎盤性抗凝固因子ANXA5遺伝子のプロモーター領域には習慣流産と関連する多型が存在するが、この多型はプロモーター領域にあるG4のコンセンサス配列を変化させる。従って、この多型が四重鎖DNAのできやすさに影響し、ANXA5の発現量が変化した結果としておこる胎盤での凝固亢進状態が習慣流産の原因であるという仮説が成り立つ。本研究では、2年間で、ANXA5のプロモーター多型と四重鎖DNA、遺伝子の発現量との関連を統合的に検討することで、習慣流産の原因を解明しようとするものである。本年度は、生体内で実際にG4構造をとっていることを証明するために、抽出したゲノムDNAに対して、熱変性をさせないバイサルファイト法をおこない、変換される塩基の割合を調べた。その結果、ANXA5遺伝子のプロモーター領域は、多の場所と比較して、変換率が高かった。また、変換されるDNA鎖とそうでない鎖が明確に分かれた。その割合がこの領域の多型と連動した。この結果から、ANXA5遺伝子のプロモーター領域は、生体内で1本鎖などの2次構造をとり、プロモーター領域の多型による遺伝子発現の多寡は、この多型の四重鎖DNAのできやすさへの影響を介している可能性が示唆された。

  • Research Products

    (17 results)

All 2015 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (5 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] ミュンスター大学(ドイツ)

    • Country Name
      GERMANY
    • Counterpart Institution
      ミュンスター大学
  • [Journal Article] TUBA1A mutation can cause a hydranencephaly-like severe form of cortical dysgenesis2015

    • Author(s)
      Yokoi S, Ishihara N, Miya F, Tsutsumi M, Yanagihara I, Fujita N, Yamamoto H, Kato M, Okamoto N, Tsunoda T, Yamasaki M, Kanemura Y, Kosaki K, Kojima S, Saitoh S, Kurahashi H, Natsume J
    • Journal Title

      Sci Rep

      Volume: 5 Pages: 15165

    • DOI

      10.1038/srep15165

    • Peer Reviewed / Open Access
  • [Journal Article] Whole genomic analysis of an unusual human G6P[14] rotavirus strain isolated from a child with diarrhea in Thailand: evidence for bovine-to-human interspecies transmission and reassortment events2015

    • Author(s)
      Tacharoenmuang R, Komoto S, Guntapong R, Ide T, Haga K, Katayama K, Kato T, Ouchi Y, Kurahashi H, Tsuji T, Sangkitporn S, Taniguchi K
    • Journal Title

      PLoS One

      Volume: 10 Pages: e0139381

    • DOI

      10.1371/journal.pone.0139381

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Emergence and characterization of unusual DS-1-like G1P[8] rotavirus strains in children with diarrhea in Thailand2015

    • Author(s)
      Komoto S, Tacharoenmuang R, Guntapong R, Ide T, Haga K, Katayama K, Kato T, Ouchi Y, Kurahashi H, Tsuji T, Sangkitporn S, Taniguchi K
    • Journal Title

      PLoS One

      Volume: 10 Pages: e0141739

    • DOI

      10.1371/journal.pone.0141739

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A unique TBX5 microdeletion with microinsertion detected in patient with Holt-Oram syndrome2015

    • Author(s)
      Morine M, Kohmoto T, Masuda K, Inagaki H, Watanabe M, Naruto T, Kurahashi H, Maeda K, Imoto I
    • Journal Title

      Am J Med Genet A

      Volume: 167 Pages: 3192-3196

    • DOI

      10.1002/ajmg.a.37359

    • Peer Reviewed
  • [Journal Article] Intragenic duplication in the PHKD1 gene in autosomal recessive polycystic kidney disease2015

    • Author(s)
      Miyazaki J, Ito M, Nishizawa H, Kato T, Minami Y, Inagaki H, Ohye T, Miyata M, Boda H, Kiriyama Y, Kuroda M, Sekiya T, Kurahashi H, Fujii T
    • Journal Title

      BMC Med Genet

      Volume: 16 Pages: 98

    • DOI

      10.1186/s12881-015-0245-3

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Preimplantation genetic diagnosis/screening by comprehensive molecular testing2015

    • Author(s)
      Kurahashi H, Kato T, Miyazaki J, Nishizawa H, Nishio E, Furukawa H, Miyamura H, Ito M, Endo T, Ouchi Y, Inagaki H, Fujii T
    • Journal Title

      Reprod Med Biol

      Volume: 15 Pages: 13-19

    • DOI

      10.1007/s12522-015-0216-6

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Nine-year follow-up in a child with chromosomal integration of human herpesvirus 6 transmitted from an unrelated donor through the Japan Marrow Donor Program2015

    • Author(s)
      Yagasaki H, Shichino H, Shimizu N, Ohye T, Kurahashi H, Yoshikawa T, Takahashi S
    • Journal Title

      Transpl Infect Dis

      Volume: 17 Pages: 160-161

    • DOI

      10.1111/tid.12338

    • Peer Reviewed
  • [Journal Article] PCSK5 mutation in a patient with the VACTERL association2015

    • Author(s)
      Nakamura Y, Kikugawa S, Seki S, Takahata M, Iwasaki N, Terai H, Matsubara M, Fujioka F, Inagaki H, Kobayashi T, Kimura T, Kurahashi H, Kato H
    • Journal Title

      BMC Res Notes

      Volume: 8 Pages: 228

    • DOI

      10.1186/s13104-015-1166-0

    • Peer Reviewed
  • [Journal Article] Novel FATP4 mutations responsible for ichthyosis prematurity syndrome in a Japanese patient2015

    • Author(s)
      Tsuge I, Morishita M, Kato T, Tsutsumi M, Inagaki H, Mori Y, Yamawaki K, Inuo C, Ieda K, Ohye T, Hayakawa A, Kurahashi H
    • Journal Title

      Human Genome Variation

      Volume: 2 Pages: 15003

    • DOI

      10.1038/hgv.2015.3

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Prenatal genetic testing for familial severe congenital protein C deficiency2015

    • Author(s)
      Tairaku S, Taniguchi-Ikeda M, Okazaki Y, Noguchi Y, Nakamachi Y, Mori T, Kubokawa I, Hayakawa A, Shibata A, Emoto T, Kurahashi H, Toda T, Kawano S, Yamada H, Morioka I, Iijima K
    • Journal Title

      Human Genome Variation

      Volume: 2 Pages: 228

    • DOI

      10.1186/s13104-015-1166-0

    • Peer Reviewed
  • [Presentation] Massive parallel sequencing revealed the conformational dynamics of the non-B form DNA at the promoter2015

    • Author(s)
      Inagaki H, Miyamura H, Tsutsumi M, Kato T, Nishizawa H, Kurahashi H
    • Organizer
      ASHG2015
    • Place of Presentation
      Baltimore
    • Year and Date
      2015-10-06 – 2015-10-10
    • Int'l Joint Research
  • [Presentation] Breakpoint analysis of the recurrent constitutional t(8;22) (q24.13;q11.21) translocation2015

    • Author(s)
      Kurahashi H, Mishra D, Kato T, Inagaki H, Kosho T, Wakui K et al.
    • Organizer
      ESHG2015
    • Place of Presentation
      Glasgow
    • Year and Date
      2015-06-06 – 2015-06-09
    • Int'l Joint Research
  • [Presentation] Deep sequencing of sodium bisulfite-treated genomic DNA revealed in vivo G-quadruplex structure affecting the gene expression of ANXA5 that causes obstetric complications.2015

    • Author(s)
      Inagaki H, Ota S, Nishizawa H, Miyamura H, Nakahira M, Suzuki M et al.
    • Organizer
      The 11th International Workshop on Advanced Genomics
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-05-20 – 2015-05-22
    • Int'l Joint Research
  • [Presentation] Breakpoint analysis of the recurrent constitutional t(8;22)(q24;q11) translocation2015

    • Author(s)
      Kato T, Inagaki H, Mishura D, Ouchi Y, Tsutsumi M, Ohye T et al.
    • Organizer
      The 11th International Workshop on Advanced Genomics
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-05-20 – 2015-05-22
    • Int'l Joint Research
  • [Presentation] Age-related increase of aneuploidy in human oocytes2015

    • Author(s)
      Kurahashi H
    • Organizer
      IFFS/JSRM International Meeting 2015
    • Place of Presentation
      Yokohama
    • Year and Date
      2015-04-26 – 2015-04-29
    • Int'l Joint Research / Invited
  • [Remarks] 藤田保健衛生大学・総合医科学研究所・分子遺伝学研究部門

    • URL

      http://www.fujita-hu.ac.jp/~genome/mg/

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Published: 2017-01-06  

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