Analysis on the involvement of the new transcriptional elongation regulator Med26 in mixed acute leukemia

• Project/Area Number: 15H04701
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Yokohama City University (2017); Hokkaido University (2015-2016)
• Principal Investigator: TAKAHASHI Hidehisa 横浜市立大学, 医学研究科, 教授 (30423544)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 遺伝子発現制御 / 転写 / 転写伸長 / がん / 急性白血病 / 発現制御 / 腫瘍性疾患 / 転写制御 / RNAポリメラーゼII / メディエーター / 腫瘍 / 遺伝子発現 / 白血病

Outline of Final Research Achievements

In this study,we addressed the mechanisms how Med26 and SEC collaborate to release the paused Pol II and clarified the mechanism of promoting tumor growth. Furthermore, we clarified how Med26 regulates the transcriptional expression of the distinct genes by recruiting two distinct transcription elongation complexes SEC and LEC.

Research Products

• [Int'l Joint Research] Stowers Institute for Medical Research(United states)
• [Int'l Joint Research] Stowers Institute for Medical Research(アメリカ合衆国)
• [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: Scientific Reports Volume: 8 Pages: 819-819
  • DOI: 10.1038/s41598-018-19198-0
  • Peer Reviewed / Open Access
• [Journal Article] Sez6l2 regulates phosphorylation of ADD and neuritogenesis. (2017)
  • Author(s): Yaguchi, H., Yabe, I., Takahashi, H., Watanabe, M., Nomura, T., Kano, T., Matsumoto, M., Nakayama, K.I., Watanabe, M. and Hatakeyama, S.
  • Journal Title: Biochem Biophys Res Commun Volume: 494 Pages: 234-241
  • DOI: 10.1016/j.bbrc.2017.10.047
  • Peer Reviewed
• [Journal Article] The novel heart-specific RING finger protein 207 regulates energy metabolism in cardiomyocytes (2016)
  • Author(s): Mizushima, W., Takahashi , H., Watanabe, M., Kinugawa, S., Matsushima, S., Takada, S., Yokota, T., Furihata, T., Matsumoto, J., Tsuda, M., Chiba, I., Nagashima, S., Yanagi, S., Matsumoto, M., Nakayama, K.I., Tsutsui, H. and Hatakeyama, S.
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 100 Pages: 43-53
  • DOI: 10.1016/j.yjmcc.2016.09.013
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] p53 represses the transcription of snRNA genes by preventing the formation of little elongation complex. (2016)
  • Author(s): Anwar, D., Takahashia, H., Watanabe, M., Suzuki, M., Fukuda, S., Hatakeyama, S.
  • Journal Title: BBA Gene Regulatory Mechanisms Volume: 1859 Pages: 975-982
  • DOI: 10.1016/j.bbagrm.2016.06.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Autoantibodies against a complement component 1 q subcomponent contribute to complement activation and recurrent thrombosis/pregnancy morbidity in anti-phospholipid syndrome. (2016)
  • Author(s): Fujieda Y., Amengual O., Matsumoto M., Kuroki K., Takahashi H., Kono M., Kurita Y., Otomo K., Kato M., Oku K., Bohgaki T., Horita T., Yasuda S., Maenaka K., Hatakeyama S., Nakayama K.I. and Atsumi T. et al.
  • Journal Title: Rheumatology (Oxford) Volume: 印刷中 Pages: 1117-1126
  • DOI: 10.1093/rheumatology/kew005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TRIM39 negatively regulates the NFkB-mediated signaling pathway through stabilization of cactin. (2016)
  • Author(s): Suzuki M, Watanabe M, Nakamaru Y, Takagi D, Takahashi H, Fukuda S, Hatakeyama S.
  • Journal Title: Cellular and Molecular Life Sciences Volume: ７３ Pages: 1085-1101
  • DOI: 10.1007/s00018-015-2040-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Chd5 regulates MuERV-L/MERVL expression in mouse embryonic stem cells via H3K27me3 modification and histone H3.1/H3.2. (2016)
  • Author(s): Hayashi M, Maehara K, Harada A, Semba Y, Kudo K, Takahashi H, Oki S, Meno C, Ichiyanagi K, Akashi K, Ohkawa Y
  • Journal Title: J. Cell. Biochem. Volume: 117 Pages: 780-792
  • DOI: 10.1002/jcb.25368
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ribophorin II is involved in the tissue factor expression mediated by phosphatidylserine-dependent antiprothrombin antibody on monocytes. (2016)
  • Author(s): Fujieda Y., Amengual O., Matsumoto M., Kuroki K., Takahashi H., Kono M., Kurita Y., Otomo K., Kato M., Oku K., Bohgaki T., Horita T., Yasuda S., Maenaka K., Hatakeyama S., Nakayama K.I. and Atsumi T. et al.
  • Journal Title: Rheumatology Volume: In press
  • Peer Reviewed
• [Journal Article] MED26 regulates the transcription of snRNA genes through the recruitment of little elongation complex. (2015)
  • Author(s): Takahashi, H., Takigawa, I., Watanabe, M., Anwar, D., Shibata, M., Tomomori-Sato, C., Sato, S., Ranjan, A., Seidel, C.W., Tsukiyama, T., Mizushima, W., Hayashi, M., Ohkawa, Y., Conaway, J.W., Conaway, R.C. and Hatakeyama, S
  • Journal Title: Nature Communications Volume: 5 Pages: 1-15
  • DOI: 10.1038/ncomms6941
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Molecular role of RNF43 in canonical and noncanonical Wnt signaling. (2015)
  • Author(s): T. Tsukiyama,et al.
  • Journal Title: Molecular and Cellular Biology Volume: in press Pages: 2007-2023
  • DOI: 10.1128/mcb.00159-15
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ (2015)
  • Author(s): Watanabe, M., Takahashi, H., Saeki, Y., Ozaki, T., Itoh, S., Suzuki, M., Mizushima, W., Tanaka, K., and Hatakeyama, S.
  • Journal Title: eLIfe Volume: 4
  • DOI: 10.7554/elife.05615
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TRIM29 regulates the p63-mediated pathway in cervical cancer cells (2015)
  • Author(s): Masuda, Y., Takahashi, H. and Hatakeyama, S.
  • Journal Title: Biochim. Biophys. Acta-Mol. Cell Res. Volume: 1853 Pages: 2296-2305
  • DOI: 10.1016/j.bbamcr.2015.05.035
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] TRIM29 regulates the assembly of DNA repair proteins into damaged chromatin (2015)
  • Author(s): Masuda, Y., Takahashi, H., Sato, S., Tomonori-Sato, C., Saraf, A., Washburn, M.P., Florens, L., Conaway, R.C., Conaway, J.W. and Hatakeyama, S.
  • Journal Title: Nature communications Volume: 6 Pages: 7299-7299
  • DOI: 10.1038/ncomms8299
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Human Mediator subunit MED26 plays a role in 3’-end processing of replication dependent Histone mRNA through recruitment of little elongation complex (2017)
  • Author(s): Hidehisa Takahashi, Mio Shibata, Ichigaku Takigawa, Masashi Watanabe, Junichi Yamamoto, Yuki Yamaguchi, Joan W. Conaway, Ronald C. Conaway, Shigetsugu Hatakeyama
  • Organizer: CSHL meeting on Mechanisms of Eukaryotic Transcription, Cold Spring Harbor Laboratory
  • 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 (2017)
  • Author(s): 高橋秀尚，柴田美音，瀧川一学，渡部昌，築山忠維，藤井聡，飯田緑，山本淳一，山口雄輝，Amol Ranjan，Shigeo Sato，Chieri-tomomori Sato，Joan W. Conaway，Ronald C. Conaway，畠山鎮次
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Regulation of transcription termination by Human Mediator complex (2016)
  • Author(s): 高橋秀尚，畠山鎮次
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] メディエーター複合体による転写制御機構 (2016)
  • Author(s): 高橋秀尚，畠山鎮次
  • Organizer: 日本生化学会
  • Place of Presentation: 東北大学川内北キャンパス（宮城県 仙台市）
  • Year and Date: 2016-09-25
• [Presentation] Role of Human Mediator Subunit Med26 in Transcription Elongation (2015)
  • Author(s): Hidehisa Takahashi, Joan W. Conaway, Ronald C. Conaway, Shigetsugu Hatakeyama
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸ポートピアホテル（兵庫県、神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] MED26 regulates the transcription of snRNA genes through the recruitment of little elongation complex (2015)
  • Author(s): Hidehisa Takahashi, Ichigaku Takigawa, Masashi Watanabe, Delnur Anwar, Mio Shibata, Chieri Tomomori-Sato, Shigeo Sato, Amol Ranjan, Chris W. Seidel, Tadasuke Tsukiyama, Wataru Mizushima, Joan W. Conaway, Ronald C. Conaway, Shigetsugu Hatakeyama.
  • Organizer: Mechanism of Eukaryotic Transcription
  • Place of Presentation: Cold spring harbor laboratory（NY, USA）
  • Year and Date: 2015-08-25
  • Int'l Joint Research
• [Presentation] Med26はLittle elongation complexをリクルートすることでsmall nuclear RNA遺伝子の発現を制御する (2015)
  • Author(s): 高橋秀尚, 畠山鎮次
  • Organizer: 第17回日本RNA学会年会
  • Place of Presentation: ホテルライフォート札幌（北海道札幌市中央区）
  • Year and Date: 2015-07-15
  • Invited