Elucidation of the relation between novel transcription regulation by Med26 and the onset of neoplastic disease

• Project/Area Number: 18H02378
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Yokohama City University
• Principal Investigator: TAKAHASHI Hidehisa 横浜市立大学, 医学研究科, 教授 (30423544)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 遺伝子発現制御 / 転写 / RNAポリメラーゼII / メディエーター複合体 / 転写伸長 / 転写終結 / 腫瘍 / メディエーター / 転写制御 / 腫瘍性疾患

Outline of Final Research Achievements

Protein-encoding genes and non-coding RNA genes are transcribed by RNA polymerase II (Pol II). We have found that the human Mediator subunit Med26 uses two different transcription elongation complexes, Super elongation complex (SEC) and Little elongation complex (LEC), to regulate different types of genes by Pol II. In this study, we found that Med26 and SEC regulate the transcription of mRNA with poly A, while Med26 and LEC regulate the transcription of genes without poly A.

Academic Significance and Societal Importance of the Research Achievements

本研究で、Med26がSECとLECを使い分けることによって転写開始後のプロセス（転写伸長、転写終結）を制御し、mRNAのポリA付加を決定していることが明らかとなれば、遺伝子発現制御の研究分野においてブレークスルーの１つとなることが期待できる。また、Med26はがんや白血病などの腫瘍性疾患の原因となっていることも予想され、本研究による将来の臨床医学への貢献も期待できる。

Research Products

• [Int'l Joint Research] ストワーズ医学研究所(米国)
• [Int'l Joint Research] ストワーズ医学研究所(米国)
• [Journal Article] Gain-of-Function MN1 Truncation Variants Cause a Recognizable Syndrome with Craniofacial and Brain Abnormalities (2020)
  • Author(s): Miyake Noriko et al., Matsumoto Naomichi
  • Journal Title: The American Journal of Human Genetics Volume: 106 Issue: 1 Pages: 13-25
  • DOI: 10.1016/j.ajhg.2019.11.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The role of Mediator and Little Elongation Complex in transcription termination (2020)
  • Author(s): Takahashi H, Ranjan A, Chen S, Suzuki H, Shibata M, Hirose T, Hirose H, Sasaki K, Abe R, Chen K, He Y, Zhang Y, Takigawa I, Tsukiyama T, Watanabe M, Fujii S, Iida M, Yamamoto J, Yamaguchi Y, Suzuki Y, Matsumoto M, Nakayama KI, Washburn P, Saraf A, Florens L, Sato S, Tomomori-Sato C, Conaway RC, Conaway JW, Hatakeyama S
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 1-20
  • DOI: 10.1038/s41467-020-14849-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Shank2 Binds to aPKC and Controls Tight Junction Formation with Rap1 Signaling during Establishment of Epithelial Cell Polarity (2020)
  • Author(s): Sasaki Kazunori、Kojitani Noriko、Hirose Hiroko、Yoshihama Yohei、Suzuki Hidefumi、Shimada Miho、Takayanagi Ayumi、Yamashita Akio、Nakaya Masa-aki、Hirano Hisashi、Takahashi Hidehisa、Ohno Shigeo
  • Journal Title: Cell Reports Volume: 31 Issue: 1 Pages: 107407-107407
  • DOI: 10.1016/j.celrep.2020.02.088
  • Peer Reviewed / Open Access
• [Journal Article] NONO is a negative regulator for SOX2 promoter. (2020)
  • Author(s): Liang S, Takahashi H, Hirose T, Kuramitsu Y, Hatakeyama S, Yoshiyama H, Wang R, Hamada J, Iizasa H.
  • Journal Title: Cancer Genomics & Proteomics Volume: 17 Issue: 4 Pages: 359-367
  • DOI: 10.21873/cgp.20195
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bromodomain-containing protein 4 regulates interleukin-34 expression in mouse ovarian cancer cells (2020)
  • Author(s): Han Nanumi、Anwar Delnur、Hama Naoki、Kobayashi Takuto、Suzuki Hidefumi、Takahashi Hidehisa、Wada Haruka、Otsuka Ryo、Baghdadi Muhammad、Seino Ken-ichiro
  • Journal Title: Inflammation and Regeneration Volume: 40 Issue: 1 Pages: 25-26
  • DOI: 10.1186/s41232-020-00129-4
  • Peer Reviewed / Open Access
• [Journal Article] A phospho-switch controls RNF43-mediated degradation of Wnt receptors to suppress tumorigenesis (2020)
  • Author(s): Tsukiyama Tadasuke、Zou Juqi、Kim Jihoon、Ogamino Shohei、Shino Yuki、Masuda Takamasa、Merenda Alessandra、Matsumoto Masaki、Fujioka Yoichiro、Hirose Tomonori、Terai Sayuri、Takahashi Hidehisa、Ishitani Tohru、Nakayama Keiichi I.、Ohba Yusuke、Koo Bon-Kyoung、Hatakeyama Shigetsugu
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 1-16
  • DOI: 10.1038/s41467-020-18257-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A substrate-trapping strategy to find E3 ubiquitin ligase substrates identifies Parkin and TRIM28 targets (2020)
  • Author(s): Watanabe Masashi、Saeki Yasushi、Takahashi Hidehisa、Ohtake Fumiaki、Yoshida Yukiko、Kasuga Yusuke、Kondo Takeshi、Yaguchi Hiroaki、Suzuki Masanobu、Ishida Hiroki、Tanaka Keiji、Hatakeyama Shigetsugu
  • Journal Title: Communications Biology Volume: 3 Issue: 1 Pages: 592-592
  • DOI: 10.1038/s42003-020-01328-y
  • Peer Reviewed / Open Access
• [Journal Article] Loss of TRIM29 Alters Keratin Distribution to Promote Cell Invasion in Squamous Cell Carcinoma. (2018)
  • Author(s): Yanagi T, Watanabe M, Hata H, Kitamura S, Imafuku K, Yanagi H, Homma A, Wang L, Takahashi H, Shimizu H, Hatakeyama S.
  • Journal Title: Cancer Res Volume: 78 Issue: 24 Pages: 6795-6806
  • DOI: 10.1158/0008-5472.can-18-1495
  • Peer Reviewed
• [Journal Article] Anti-Sez6l2 antibody, detected in a patient with immune-mediated cerebellar ataxia, inhibits complex formation of GluR1 and Sez6l2 (2018)
  • Author(s): Yaguchi, H., Yabe, I., Takahashi, H., Watanabe, M., Nomura, T., Kano, T., Watanabe, M. and Hatakeyama, S.
  • Journal Title: J. Neurol. Volume: 265 Issue: 4 Pages: 962-965
  • DOI: 10.1007/s00415-018-8785-z
  • Peer Reviewed
• [Journal Article] Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome (2018)
  • Author(s): Yabe I, Yaguchi H, Kato Y, Miki Y, Takahashi H, Tanikawa S, Shirai S, Takahashi I, Kimura M, Hama Y, Matsushima M, Fujioka S, Kano T, Watanabe M, Nakagawa S, Kunieda Y, Ikeda Y, Hasegawa M, Nishihara H, Ohtsuka T, Tanaka S, Tsuboi Y, Hatakeyama S, Wakabayashi K, Sasaki H
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 819-819
  • DOI: 10.1038/s41598-018-19198-0
  • NAID: 120006377499
  • Peer Reviewed / Open Access
• [Journal Article] Brain-Derived Neurotrophic Factor Improves Limited Exercise Capacity in Mice With Heart Failure (2018)
  • Author(s): Matsumoto Junichi、et al. Hatakeyama Shigetsugu、Matsumoto Masaki、Nakayama Keiichi I.、Otsuka Yutaro、Sabe Hisataka、Tsutsui Hiroyuki、Anzai Toshihisa
  • Journal Title: Circulation Volume: 138 Issue: 18 Pages: 2064-2066
  • DOI: 10.1161/circulationaha.118.035212
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] メディエーター複合体による転写終結制御機構の解明 (2019)
  • Author(s): 高橋 秀尚, Amol Ranjan, 鈴木 秀文, 阿部 竜太, 廣瀬 智威, 佐々木 和教, 山口 雄輝, 中山 敬一, Joan Conaway, Ronald Conaway, 畠山 鎮次
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] メディエーターは2つの異なる核内凝集体を結びつけることによって転写終結を制御する (2019)
  • Author(s): 鈴木 秀文, 阿部 竜太, 安井 七海, 高橋 秀尚
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] クロマチン構造変換を伴った遺伝子発現制御機構 (2019)
  • Author(s): 嶋田 美穂, 中太 智義, 高橋 秀尚, Robert G.Roeder
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] メディエーター複合体による転写制御機構の解明 (2019)
  • Author(s): 高橋 秀尚
  • Organizer: 第91回日本遺伝学会
  • Invited
• [Presentation] The role of Mediator in transcription termination. (2018)
  • Author(s): Takahashi H, Amol Ranjan, Shiyuan Chen, Shibata M, Takigawa I, Watanabe M, Tsukiyama T, Fujii S, Yamamoto J, Yamaguchi Y, Matsumoto M, Nakayama K, Suzuki Y, Sato C, Sato S, Ronald C. Conaway, Joan W. Conaway, Hatakeyama S:
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] メディエーター複合体のサブユニットMED26による転写制御機構 (2018)
  • Author(s): 高橋 秀尚
  • Organizer: 第12回日本エピジェネティクス研究会年会
  • Invited
• [Remarks] https://ycu-molecularbiology.jp/
• [Remarks] ホームページ
  • URL: https://ycu-molecularbiology.jp/
• [Remarks] 横浜市立大学・大学院医学研究科・分子細胞生物学教室
  • URL: https://ycu-molecularbiology.jp/