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Analysis of action mechanism of endocrine-disruptors targeting epigenetic memory

Research Project

Project/Area Number 25340046
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionShizuoka University

Principal Investigator

YAMAUCHI Kiyoshi  静岡大学, グリーン科学技術研究所, 教授 (50201827)

Co-Investigator(Kenkyū-buntansha) ISHIHARA Akinori  静岡大学, 理学部, 講師 (70432193)
NISHIYAMA Norihito  福島県立医科大学, 医学部, 講師 (10315666)
Co-Investigator(Renkei-kenkyūsha) MOCHIZUKI Kazuki  山梨大学, 生命環境学部, 准教授 (80423838)
Research Collaborator OTSUKA Shunsuke  
IZUMI Yushi  
KASAI Kentaro  
TAMAOKI Keiji  
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords甲状腺ホルモン / ホルモン応答遺伝子 / 撹乱化学物質 / エピジェネティック作用 / ヒストン修飾 / RNAポリメラーゼII
Outline of Final Research Achievements

Thyroid hormones (THs) play important roles in growth, development, differentiation, and metabolism in vertebrates. To elucidate molecular mechanisms by which environmental chemicals exert TH-disrupting activity, we investigated their effects on the histone and RNA polymerase II (RNAPII) modifications and DNA methylation status in two direct TH-response genes in amphibian TH-responsive cultured cells. For both genes, TH enhanced the amounts of gene transcripts and increased the amounts of epigenetic marks of transcription activation. Treatment with the chemicals reduced the amounts of the gene transcript and suppressed some of the T3-induced epigenetic marks. However, the 5' regulatory region remained to be hypermethylated even with exposure to TH. Our results demonstrate that the chemicals affect TH-induced histone and RNAPII modifications in direct TH-response genes, in somewhat target gene-dependent and chemical-specific manners.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (23 results)

All 2016 2015 2014 2013 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Acknowledgement Compliant: 4 results,  Open Access: 2 results) Presentation (9 results) Book (1 results) Remarks (5 results)

  • [Journal Article] Morphological, biochemical, transcriptional and epigenetic responses to fasting and refeeding in intestine of Xenopus laevis.2016

    • Author(s)
      Tamaoki, K., Okada, R., Ishihara, A., Shiojiri, N., Mochizuki, K., Goda, T., Yamauchi, K.
    • Journal Title

      Cell Biosci.

      Volume: 6 Issue: 1 Pages: 2-2

    • DOI

      10.1186/s13578-016-0067-9

    • NAID

      120005698530

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cold temperature blocks thyroid hormone-induced changes in lipid and energy metabolism in the liver of Lithobates catesbeianus tadpoles.2016

    • Author(s)
      Suzuki, S., Awai, K., Ishihara, A., Yamauchi, K.
    • Journal Title

      Cell Biosci.

      Volume: 6 Issue: 1 Pages: 19-19

    • DOI

      10.1186/s13578-016-0087-5

    • NAID

      120005746311

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Characterization of little skate (Leucoraja erinacea) recombinant transthyretin: zinc-dependent 3,3',5-triiodo-L-thyronine binding.2015

    • Author(s)
      Suzuki S, Kasai K, Yamauchi K.
    • Journal Title

      Gen. Comp. Endocrinol.

      Volume: 217-218 Pages: 43-53

    • DOI

      10.1016/j.ygcen.2015.04.006

    • NAID

      120005746313

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Exposure to 3, 3', 5-triiodothyronine affects histone and RNA polymerase II modifications, but not DNA methylation status, in the regulatory region of the Xenopus laevis thyroid hormone receptor beta A gene.2015

    • Author(s)
      Kasai K, Nishiyama N, Izumi Y, Otsuka S, Ishihara A, Yamauchi K
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 467 Issue: 1 Pages: 33-38

    • DOI

      10.1016/j.bbrc.2015.09.132

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Histochemical Analyses of Biliary Development During Metamorphosis of Xenopus laevis Tadpoles.2015

    • Author(s)
      Ueno T, Ishihara A, Yagi S, Koike T, Yamauchi K, Shiojiri N.
    • Journal Title

      Zoolog Sci.

      Volume: 32 Issue: 1 Pages: 88-96

    • DOI

      10.2108/zs140104

    • NAID

      40020363863

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ioxynil and Tetrabromobisphenol A Suppress Thyroid Hormone-Induced Activation of Transcriptional Elongation Mediated by Histone Modifications and RNA Polymerase II Phosphorylation.2014

    • Author(s)
      Otsuka, S., Ishihara, A., and Yamauchi, K.
    • Journal Title

      The Toxicological Sciences

      Volume: 138 Issue: 2 Pages: 290-29

    • DOI

      10.1093/toxsci/kfu012

    • NAID

      120005550335

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of Japanese herbal crude drug, combined extract of Sasa albo-margina leaves, Japanese red pine leaves and ginseng roots on gene expression in hypercholesterolemic rat liver.2013

    • Author(s)
      Ishihara, A., Takahashi, R., Numajiri T., Kaneko, S., Ishizawa Y., Koya, S., Yamauchi, K.
    • Journal Title

      Journal of Traditional Medicines

      Volume: 30 Pages: 236-245

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of Oncorhynchus mykiss 5-hydroxyisourate hydrolase/transthyretin superfamily: Evolutionary and functional analyses.2013

    • Author(s)
      Kasai K, Nishiyama N, Yamauchi K.
    • Journal Title

      Gene

      Volume: 531 Issue: 2 Pages: 326-336

    • DOI

      10.1016/j.gene.2013.08.071

    • NAID

      120005350527

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Effects of thyroid hormone on the epigenetic changes in the regulatory region of the Xenopus laevis thyroid hormone receptor gene.2015

    • Author(s)
      Nishiyama N, Kasai K, Izumi Y, Otsuka S, Ishihra A, Yamauchi K.
    • Organizer
      CompBiol 2015 (第40回日本比較内分泌学会大会)
    • Place of Presentation
      JMSアステールプラザ (広島)
    • Year and Date
      2015-12-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] Molecular mechanisms of thyroid hormone-induced chromatin modifications and the effects of cold stress on the expression of thyroid hormone responsive genes.2014

    • Author(s)
      Yamauchi K
    • Organizer
      The 8th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology
    • Place of Presentation
      Okazaki, Aichi, National Institute for Basic Biology
    • Year and Date
      2014-11-07 – 2014-11-09
    • Related Report
      2014 Research-status Report
  • [Presentation] Effects of environmental chemicals on thyroid hormone-dependent modifications of hoistone and RNA polymerase II.2014

    • Author(s)
      Akinori Ishihara and Kiyoshi Yamauchi
    • Organizer
      The 8th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology
    • Place of Presentation
      Okazaki, Aichi, National Institute for Basic Biology
    • Year and Date
      2014-11-07 – 2014-11-09
    • Related Report
      2014 Research-status Report
  • [Presentation] アフリカツメガエルを用いた消化管の絶食/再摂食に対する応答の検討2014

    • Author(s)
      玉置啓二、岡田令子,石原顕紀、望月和樹,山内清志
    • Organizer
      日本動物学会 第85回大会
    • Place of Presentation
      仙台・宮城県・東北大学
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 円口類ヌタウナギの甲状腺ホルモン結合タンパクの機能解析2014

    • Author(s)
      笠井謙太郎,鈴木駿介,西山学即,山内清志
    • Organizer
      日本動物学会 第85回大会
    • Place of Presentation
      仙台・宮城県・東北大学
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] ウシガエル生体膜の低温応答機構の解析2014

    • Author(s)
      鈴木駿介,石原顕紀、粟井光一郎,山内清志
    • Organizer
      日本動物学会 第85回大会
    • Place of Presentation
      仙台・宮城県・東北大学
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 環境化学物質がアフリカツメガエル甲状腺系に及ぼすエピジェネティック作用の検証2014

    • Author(s)
      泉勇志,石原顕紀、山内清志
    • Organizer
      日本動物学会 第85回大会
    • Place of Presentation
      仙台・宮城県・東北大学
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 甲状腺ホルモン依存的なヒストン修飾及びRNAポリメラーゼII活性に及ぼす環境化学物質の影響2013

    • Author(s)
      大塚駿介、石原顕紀、山内清志
    • Organizer
      第16回環境ホルモン学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 環境化学物質が甲状腺系に及ぼすエピジェネティックな影響の解析2013

    • Author(s)
      大塚駿介,石原顕紀,山内清志
    • Organizer
      日本動物学会第84回大会
    • Place of Presentation
      岡山
    • Related Report
      2013 Research-status Report
  • [Book] Handbook of Hormones, Comparative Endocrinology for Basic and Clinical Research2015

    • Author(s)
      Takei, Y., Ando, H., Tsutsui, K.
    • Total Pages
      674
    • Publisher
      Academic Press
    • Related Report
      2015 Annual Research Report
  • [Remarks] 静岡大学グリーン科学技術研究所グリーンバイオ研究部門環境分子生物学研究室

    • URL

      http://www.ipc.shizuoka.ac.jp/~sbkyama/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 静岡大学グリーン科学技術研究所・グリーンバイオ研究部門・環境分子生物学研究室

    • URL

      http://www.ipc.shizuoka.ac.jp/~sbkyama/

    • Related Report
      2014 Research-status Report
  • [Remarks] 静岡大学グリーン科学技術研究所クリーンバイオ部門 環境分子生物学研究室

    • URL

      http://www.ipc.shizuoka.ac.jp/~sbkyama/

    • Related Report
      2013 Research-status Report
  • [Remarks] 静岡大学教員データベース

    • URL

      https://tdb.shizuoka.ac.jp/RDB/public/Default2.aspx?id=11016&l=0

    • Related Report
      2013 Research-status Report
  • [Remarks] 静岡大学グリーン科学技術研究所グリーンバイオ研究部門

    • URL

      http://www.green.shizuoka.ac.jp/lab_staff00012.html

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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