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Promoter analysis of sweet and umami taste receptor genes

Research Project

Project/Area Number 16K11455
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Morphological basic dentistry
Research InstitutionKyushu Dental College

Principal Investigator

Toyono Takashi  九州歯科大学, 歯学部, 准教授 (10311929)

Co-Investigator(Kenkyū-buntansha) 中富 満城  九州歯科大学, 歯学部, 講師 (10571771)
片岡 真司  九州歯科大学, 歯学部, 助教 (80364149)
瀬田 祐司  九州歯科大学, 歯学部, 教授 (90291616)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords転写 / Tas1r1 / Klf5 / プロモーター / うま味 / 転写因子 / 味覚受容体 / 転写調節 / KLF5 / アミノ酸 / T1R1 / T1R3 / 甘味受容体 / うま味受容体 / 転写制御
Outline of Final Research Achievements

In this study, we examined the function of Tas1r1 promoter in the mouse C2C12 myoblasts. Reporter assays showed that a 148-bp region upstream of the start codon of Tas1r1 had a promoter activity. Site-directed mutagenesis of GT-box in this promoter significantly reduced the promoter activation. RNAi-mediated depletion of Sp4 and Klf5 decreased Tas1r1 expression. The overexpression of Klf5, but not Sp4, significantly increased Tas1r1 expression. The ENCODE data of chromatin immunoprecipitation and sequencing (ChIP-seq) showed that Klf5 bound to the GT-box. Furthermore, the Klf5 knockout cell lines led to a considerable decrease in the levels of Tas1r1 expression. Taken together, these results showed that Klf5 binds to the GT-box in the Tas1r1 promoter and regulates Tas1r1 expression in C2C12 cells.

Academic Significance and Societal Importance of the Research Achievements

高齢者に多い感覚器障害の一つであり、味覚障害を予防、治療することは、高齢者におけるQOLの維持を考える上で重要であると考えられる。味覚受容体発現の低下が認められる味覚障害患者においては、甘味、うま味受容体T1Rファミリーの転写を活性化させる転写因子が、機能不全に陥っている可能性が考えられる。本研究により、うま味受容体Tas1r1遺伝子の転写の活性化に、転写因子Klf5が関与していることが明らかになった。転写の活性化には、複数の転写因子が関わっていることから、本研究を端緒として、他の転写因子を含めた転写活性化機構が明らかになれば、その機能不全のメカニズムの解明にもつながると考えられる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (24 results)

All 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (17 results) (of which Int'l Joint Research: 3 results) Remarks (1 results)

  • [Journal Article] Krüppel-like factor 5 (Klf5) regulates expression of mouse T1R1 amino acid receptor gene (<i>Tas1r1</i>) in C2C12 myoblast cells2019

    • Author(s)
      HIRATA Yuki、TOYONO Takashi、KOKABU Shoichiro、OBIKANE Yui、KATAOKA Shinji、NAKATOMI Mitsushiro、MASAKI Chihiro、HOSOKAWA Ryuji、SETA Yuji
    • Journal Title

      Biomedical Research

      Volume: 40 Issue: 2 Pages: 67-78

    • DOI

      10.2220/biomedres.40.67

    • NAID

      130007632092

    • ISSN
      0388-6107, 1880-313X
    • Year and Date
      2019-04-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anticancer effect of novel platinum nanocomposite beads on oral squamous cell carcinoma cells2019

    • Author(s)
      Tanaka M., Okinaga T., Iwanaga K., Matsuo K., Toyono T., Sasaguri M., Ariyoshi W., Tominaga K., Enomoto Y., Matsumura Y., Nishihara, T.
    • Journal Title

      J Biomed Mater Res B Appl Biomater

      Volume: 9999B Issue: 7 Pages: 1-7

    • DOI

      10.1002/jbm.b.34320

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hey1 and Hey2 are differently expressed during mouse tooth development.2018

    • Author(s)
      Kibe K, Nakatomi M, Kataoka S, Toyono T, Seta Y.
    • Journal Title

      Gene Expression Patterns

      Volume: 27 Pages: 99-105

    • DOI

      10.1016/j.gep.2017.11.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] On the Emerging Role of the Taste Receptor Type 1 (T1R) Family of Nutrient-Sensors in the Musculoskeletal System2017

    • Author(s)
      S. Kokabu, J.W. Lowery, T. Toyono, T. Sato, T. Yoda,
    • Journal Title

      Molecules

      Volume: 22 Issue: 3 Pages: 1-7

    • DOI

      10.3390/molecules22030469

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cutaneous pigmentation modulates skin sensitivity via tyrosinase-dependent dopaminergic signalling2017

    • Author(s)
      Ono Kentaro、Viet Chi T.、Ye Yi、Dang Dongmin、Hitomi Suzuro、Toyono Takashi、Inenaga Kiyotoshi、Dolan John C.、Schmidt Brian L.Ono K, Viet CT, Ye Y, Dang D, Hitomi S, Toyono T, Inenaga K, Dolan JC, Schmidt BL
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 9181-9181

    • DOI

      10.1038/s41598-017-09682-4

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression of N-cadherin and cell surface molecules in the taste buds of mouse circumvallate papillae.2017

    • Author(s)
      Matsuyama K, Seta Y, Kataoka S, Nakatomi M, Toyono T, Kawamoto T
    • Journal Title

      Journal of Oral Biosciences

      Volume: 59 Issue: 4 Pages: 218-223

    • DOI

      10.1016/j.job.2017.09.002

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] マウスアミノ酸受容体T1R1遺伝子における転写因子Tbx3の機能解析2018

    • Author(s)
      豊野 孝, 片岡真司, 中富満城, 瀬田祐司
    • Organizer
      第78回九州歯科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Msx1遺伝子変異と低酸素負荷の複合作用による口蓋裂発症機構の解析2018

    • Author(s)
      朴 真実, 中富満城, 笹栗正明, 土生 学, 片岡 真司, 豊野 孝, 瀬田 祐司, 冨永 和宏
    • Organizer
      第78回九州歯科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] マウスT1R1遺伝子の転写調節におけるKLF5の機能解析2018

    • Author(s)
      豊野 孝,片岡真司,中富満城,瀬田祐司
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 胎生期の低酸素負荷による口唇口蓋裂発症機構の解析2018

    • Author(s)
      中富満城,片岡真司,豊野孝,瀬田祐司
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] マウスアミノ酸受容体T1R1遺伝子の転写調節におけるKLF5の機能解析2018

    • Author(s)
      豊野 孝,片岡真司,中富満城,瀬田祐司
    • Organizer
      第74回日本解剖学会九州支部学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 口唇裂発症モデルマウスにおける遺伝-環境相互作用の解析2018

    • Author(s)
      中富満城,片岡真司,豊野孝,瀬田祐司
    • Organizer
      第74回日本解剖学会九州支部学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] KLF5 promotes expression of the mouse T1R1 amino acid (umami) receptor gene (Tas1r1) in C2C12 cells.2018

    • Author(s)
      Takashi Toyono, Yuki Hirata, Yui Obikane, Shinji Kataoka, Mitsushiro Nakatomi and Yuji Seta
    • Organizer
      17th international Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ゲノム編集法を用いたマウスアミノ酸受容体T1R1遺伝子の転写調節における転写因子Tbx3の機能解析.2018

    • Author(s)
      豊野孝,平田祐基,片岡真司,中富満城,瀬田祐司
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 筋芽細胞株C2C12における、転写因子KLF2によるアミノ酸(うま味)受容体T1R1遺伝子の転写調節機構の解析2017

    • Author(s)
      豊野 孝,平田 祐基,片岡 真司,中富 満城, 細川 隆司, 瀬田 祐司
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Place of Presentation
      長崎
    • Year and Date
      2017-03-27
    • Related Report
      2016 Research-status Report
  • [Presentation] romoter Analysis for the Mouse Amino Acids Receptor T1R1 Gene.2017

    • Author(s)
      Yuki Hirata, Takashi Toyono, Chihiro Masaki, Ryuji Hosokawa, Yuji Seta,
    • Organizer
      IADR/AADR/CADR GENERAL SESSION & EXHIBITION.
    • Place of Presentation
      San Francisco
    • Year and Date
      2017-03-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Promoter analysis for mouse T1R1 amino acids (umami) receptor gene in C2C12 cells.2017

    • Author(s)
      Takashi Toyono, Yuki Hirata, Shinji Kataoka, Mitsushiro Nakatomi, Yuji Seta
    • Organizer
      16th international Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception.
    • Related Report
      2017 Research-status Report
  • [Presentation] C2C12におけるアミノ酸受容体T1R1遺伝子の転写調節機構の解析.2017

    • Author(s)
      平田 祐基,豊野 孝,細川 隆司,瀬田 祐司
    • Organizer
      第77回九州歯科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] DNAアフィニティ沈降法を用いたマウスうま味(アミノ酸)受容体T1R1遺伝子の転写調節機構の解析.2017

    • Author(s)
      豊野孝,平田祐基,片岡真司,中富満城,瀬田祐司
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 筋芽細胞株C2C12における,アミノ酸(うま味)受容体T1R1遺伝子の転写調節機構の解析2017

    • Author(s)
      平田祐基,豊野孝,細川隆司,瀬田祐司
    • Organizer
      平成28年度公益社団法人日本補綴歯科学会九州支部,中国・四国支部合同学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Analysis of the function of SP/KLF family in the promoter of mouse T1R1 amino acids (umami) receptor gene in C2C12 cells.2016

    • Author(s)
      Takashi Toyono, Yuki Hirata, Shinji Kataoka, Mitsushiro Nakatomi, Ryuji Hosokawa, Yuji Seta
    • Organizer
      15th international Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception
    • Place of Presentation
      Fukuoka
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 筋芽細胞株C2C12における、アミノ酸(うま味)受容体T1R1遺伝子の転写調節機構の解析2016

    • Author(s)
      平田 祐基, 豊野 孝,細川 隆司, 瀬田 祐司
    • Organizer
      日本補綴歯科学会 九州支部,中国・四国支部合同学術大会
    • Place of Presentation
      熊本
    • Year and Date
      2016-09-03
    • Related Report
      2016 Research-status Report
  • [Presentation] 筋芽細胞株C2C12の筋管細胞への分化段階における、アミノ酸(うま味)受容体T1R1遺伝子の転写調節機構の解析2016

    • Author(s)
      平田 祐基, 豊野 孝, 片岡 真司, 中富 満城, 細川 隆司, 瀬田 祐司
    • Organizer
      第76回九州歯科学会総会
    • Place of Presentation
      北九州
    • Year and Date
      2016-05-28
    • Related Report
      2016 Research-status Report
  • [Remarks] 研究者総覧

    • URL

      http://www.kyu-dent.ac.jp/docs/research/researcher/toyono.pdf

    • Related Report
      2019 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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