Unified crosstalk of signal transduction, chromatin regulation, and RNA processing by transcription complexes

2009 Fiscal Year Final Research Report

• Project/Area Number: 17054022
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: University of Toyama
• Principal Investigator: OHKUMA Yoshiaki University of Toyama, 大学院・医学薬学研究部, 教授 (70192515)
• Co-Investigator(Renkei-kenkyūsha): HIROSE Yutaka 富山大学, 大学院・医学薬学研究部, 准教授 (00218851) ; TANAKA Aki 富山大学, 大学院・医学薬学研究部, 助教 (50432109)
• Project Period (FY): 2005 – 2009
• Keywords: RNAポリメラーゼII(Pol II) / 基本転写因子TFIIH / CTD / メディエーター複合体 / リン酸化 / コファクター

Research Abstract

The applicants characterized the functions of two general transcription factors, TFIIE and TFIIH, which assist Pol II for accurate transcription, and the multisubunit Mediator complex which transduces transcriptional activation signals to Pol II in the nucleus. As for Mediator, we demonstrated that two CDK subunits play a role as a molecular switch between positive and negative regulations in transcription, and we further elucidated the molecular mechenism of TFIIH regulation by TFIIE upon binding.

Research Products

• [Journal Article] The central forkhead domain of the small subunit of TFIIE plays a primary role in double-stranded DNA binding at transcription initiation (2009)
  • Author(s): Tanaka, A., Watanabe, T., Iida, Y., Hanaoka, F., Ohkuma, Y
  • Journal Title: Genes Cells 14 Pages: 395-405
  • Peer Reviewed
• [Journal Article] Prolyl isomerase Pin1 shares functional similarity with phosphorylated CTD interacting factor PCIF1 in vertebrate cells (2009)
  • Author(s): Yunokuchi, I., Fan, H., Iwamoto, Y., Araki, C., Yuda, M., Umemura, H., Harada, F., Ohkuma, Y., Hirose, Y
  • Journal Title: Genes Cells 14 Pages: 1105-1118
  • Peer Reviewed
• [Journal Article] Structural insight into the TFIIE/TFIIH: TFIIE and p53 share the binding region on TFIIH (2008)
  • Author(s): Okuda, M., *Tanaka, A., Satoh, M., Takazawa, M., Mizuta, S., Ohkuma, Y., Nishimura, Y
  • Journal Title: EMBO J 27 Pages: 1161-1171
  • Peer Reviewed
• [Journal Article] Human Mediator Kinase Subunit CDK11 Plays a Negative Role in Viral Activator VP16-dependent Transcription (2008)
  • Author(s): Tsutsui, T., Umemura, H., Tanaka, A., Mizuki, F., Hirose, Y., Ohkuma, Y
  • Journal Title: Genes Cells 13 Pages: 817-826
  • Peer Reviewed
• [Journal Article] Human phosphorylated CTD-interacting protein, PCIF1, negatively modulates gene expression by RNA polymerase II (2008)
  • Author(s): Hirose, Y., *Iwamoto, Y., Sakuraba, K., Yunokuchi, I., Harada, F., Ohkuma, Y
  • Journal Title: Biochem. Biophys. Res. Comm 69 Pages: 449-455
  • Peer Reviewed
• [Journal Article] Structural characterization of human transcription factor TFIIF in solution (2008)
  • Author(s): Akashi, S., Nagakura, S., Yamamoto, S., Ohkuma, Y., Nishimura, Y
  • Journal Title: Protein Science 17 Pages: 389-400
  • Peer Reviewed
• [Journal Article] Mouse nucleolin binds to 4. 5S RNAh, a small noncoding RNA (2008)
  • Author(s): Hirose, Y., Harada, F
  • Journal Title: Biochem. Biophys. Res. Commun 365 Pages: 62-68
  • Peer Reviewed
• [Journal Article] A kinase subunit of the human Mediator complex, CDK8, positively regulates transcriptional activation (2007)
  • Author(s): Furumoto, T., Tanaka, A., Ito, M., Malik, S., Hirose, Y., Hanaoka, F., Ohkuma, Y
  • Journal Title: Genes Cells 12 Pages: 119-132
  • Peer Reviewed
• [Journal Article] Phosphorylation of the C-terminal domain of RNA polymerase II plays central roles in the integrated events of eukaryotic gene expression (2007)
  • Author(s): Hirose, Y., Ohkuma, Y
  • Journal Title: J. Biochem 122 Pages: 481-489
• [Journal Article] Studies of Schizosaccharomyces pombe TFIIE indicate conformational and functional changes in RNA polymerase II at transcription initiation (2005)
  • Author(s): Hayashi, K., Watanabe, T., Tanaka, A., Furumoto, T., Sato-Tsuchiya, C., Kimura, M., Yokoi, M., Ishihama, A., Hanaoka, F., Ohkuma, Y
  • Journal Title: Genes Cells 10 Pages: 207-224
  • Peer Reviewed
• [Journal Article] Structural insights into the asymmetric effects of zinc-ligand cysteine mutations in the novel zinc ribbon domain of human TFIIEα for transcription (2005)
  • Author(s): Okuda, M., Tanaka, A., Hanaoka, F., Ohkuma, Y., Nishimura, Y
  • Journal Title: J. Biochem 138 Pages: 443-449
  • Peer Reviewed
• [Journal Article] Mitogenic activity of S100A9 (MRP-14). Biol (2005)
  • Author(s): Shibata, F., Ito, A., Ohkuma, Y., Mitsui, K
  • Journal Title: Pharm. Bull 28 Pages: 2312-2314
  • Peer Reviewed
• [Presentation] 基本転写因子TFIIEによる2種のRNAポリメラーゼIICTDキナーゼ複合体の制御. シンポジウム1S14pタンパク質修飾による遺伝子発現制御のクロストーク (2009)
  • Author(s): 大熊芳明, 中坪拓也, 後藤さやか, 筒井大気, 田中亜紀
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-20091024
• [Presentation] Mediator MED15 and general transcription factor TFIIE interact to regulate RNA polymerase II transcription (2009)
  • Author(s): Nakatsubo, T., Tanaka, A., Tsutsui, T., Mizuki, F., Ohkuma, Y
  • Organizer: The 2009 CSH Meeting on Mechanisms of Eukaryotic Transcription
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 20090800
• [Presentation] Functional characterization of the vertebrate phosphorylated CTD-interacting protein PCIF1 (2009)
  • Author(s): Hirose, Y., Iwamoto, Y., Yunokuchi, I., Araki, C., Harada, H., Ho, K., Shuman, S., Mizuta, S., Ohkuma, Y
  • Organizer: The 2009 CSH Meeting on Mechanisms of Eukaryotic Transcription
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 20090800
• [Presentation] Mediator complexes play various roles in transcription (2009)
  • Author(s): Ohkuma, Y., Tsutsui, T., Umemura, H., Nakatsubo, T
  • Organizer: The 24th Naito Conference on Nuclear Dynamics and RNA [II]
  • Place of Presentation: Chateraise Gateaux Kingdom Sapporo, Sapporo, Japan
  • Year and Date: 20090600
• [Presentation] 脊椎動物リン酸化RNAポリメラーゼII制御因子の機能解析 (2009)
  • Author(s): 広瀬豊, 岩本悠, 山本真也, 荒木千里, 河野隆英, 水口峰之, 原田文夫, 大熊芳明
  • Organizer: 遺伝情報DECODE・冬のワークショップ(転写研究会共催)
  • Place of Presentation: 湯沢
  • Year and Date: 20090119-20090121
• [Presentation] Specific interaction of TFIIEα acidic domain with TFIIH p62 PH domain in regulation of initiation transcription (2008)
  • Author(s): Tanaka, A., Mizuta, S., Takazawa, M., Okuda, M., Nishimura, Y., Ohkuma, Y
  • Organizer: 8th EMBL Transcription Meeting
  • Place of Presentation: EMBL, Heidelberg, Germany
  • Year and Date: 20080823-20080827
• [Presentation] Two CDK subunits of Mediator complex play opposite roles each other in transcriptional repression (2008)
  • Author(s): Ohkuma, Y
  • Organizer: 8th EMBL Transcription Meeting
  • Place of Presentation: EMBL, Heidelberg, Germany
  • Year and Date: 20080800
• [Presentation] Functional study on novel Mediator subunit CDK11 in transcriptional regulation (2008)
  • Author(s): Tsutsui, T., Umemura, H., Tanaka, A., Mizuki, F., Hirose, Y., Ohkuma, Y
  • Organizer: 8th EMBL Transcription Meeting
  • Place of Presentation: EMBL, Heidelberg, Germany
  • Year and Date: 20080800
• [Presentation] Studies on the Mechanisms of Nuclear Signaling via Transcription Apparatus (2008)
  • Author(s): Ohkuma, Y
  • Organizer: The 21st Naito Conference on Nuclear Dynamics and RNA [I]
  • Place of Presentation: Yatsugatake Royal Hotel, Yamanashi, Japan
  • Year and Date: 20080600
• [Presentation] Functional study of novel Mediator kinase subunit CDK11 in transcriptional regulation (2008)
  • Author(s): Tsutsui T., Umemura H., Tanaka A., Mizuki F., Hirose Y., Ohkuma Y
  • Organizer: The 21st Naito Conference on Nuclear Dynamics and RNA [I]
  • Place of Presentation: Yatsugatake Royal Hotel, Yamanashi, Japan
  • Year and Date: 20080600
• [Presentation] メディエーター複合体の新規キナーゼサブユニットの機能解析 (2008)
  • Author(s): 梅村啓靖, 筒井大気, 田中亜紀, 廣瀬豊, 大熊芳明
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 20080326-20080328
• [Presentation] メディエーターの2つのCDKサブユニットCDK8とCDK11は転写において正反対に機能する (2008)
  • Author(s): 大熊芳明
  • Organizer: 北海道大学大学院薬学研究院特別講演会(共催:日本薬学会北海道支部, 日本生化学会北海道支部, 北海道分子生物学研究会)
  • Place of Presentation: 札幌
  • Year and Date: 2008-06-16
• [Presentation] 転写とDNA修復のスイッチモデルーp53と基本転写因子TFIIEによるTFIIHの受渡し (2008)
  • Author(s): 大熊芳明
  • Organizer: 「特定領域研究」2領域合同公開シンポジウム「クロマチンシグナリングの分子機構」
  • Place of Presentation: 東京
  • Year and Date: 2008-01-08
• [Presentation] 転写メディエーターから基本転写装置へのシグナリング (2007)
  • Author(s): 田中亜紀, 古元義, 廣瀬豊, 花岡文雄, 大熊芳明
  • Organizer: BMB2007ワークショップ「遺伝子発現に向けた核内シグナリング」
  • Place of Presentation: 横浜
  • Year and Date: 20071211-20071215
• [Presentation] Functional studies on TFIIE and its mediated changes of RNA polymerase II in association with TFIIH and Mediator (2007)
  • Author(s): Nakatsubo, T., Goto, S., Iida, Y., Tanaka, A., Ohkuma, Y
  • Organizer: 10th Cold Spring Harbor Meeting on Cancer Cells: mechanisms of eukaryotic transcription
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 20070800
• [Presentation] hCDK8, a kinase subunit of human Mediator complex, plays a positive role in transcription (2007)
  • Author(s): Umemura, H., Tsutsui, T., Nakatsubo, T., Tanaka, A., Hirose, Y., Ohkuma, Y
  • Organizer: 10th Cold Spring Harbor Meeting on Cancer Cells
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 20070800
• [Presentation] ヒトメディエーター複合体のキナーゼサブユニットCDK8は転写活性化を正に制御する (2007)
  • Author(s): 大熊芳明, 古元義, 田中亜紀, 花岡文雄
  • Organizer: 日本薬学会第127年会 シンポジウム「核内情報受容から遺伝子発現への機構-その分子レベルでのアプローチ」
  • Place of Presentation: 富山
  • Year and Date: 20070328-20070330
• [Presentation] リン酸化RNAポリメラーゼII結合因子PCIF1による脊椎動物遺伝子発現調節 (2007)
  • Author(s): 廣瀬豊, 荒木千里, 范紅, 湯の口いずみ, 湯田昌道, 原田文夫, 大熊芳明
  • Organizer: 日本薬学会第127年会 シンポジウム「核内情報受容から遺伝子発現への機構-その分子レベルでのアプローチ」
  • Place of Presentation: 富山
  • Year and Date: 20070328-20070330
• [Presentation] 遺伝子発現におけるRNAポリメラーゼIIの制御 (2007)
  • Author(s): 大熊芳明
  • Organizer: 第7回転写研究会冬のワークショップ
  • Place of Presentation: 新潟
  • Year and Date: 20070100
• [Presentation] The Roles of Conformational Changes in Transcription Complexes (2007)
  • Author(s): Ohkuma, Y
  • Organizer: International Symposium on Systems Biology Initiative at University of Tokyo
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2007-11-18
• [Presentation] Functional characterization of the phosphorylated RNA polymerase II interacting factor PCIF1 (2006)
  • Author(s): Hirose, Y., Araki, C., Yuda, M., Yunokuchi, I., Fan, H., Harada, F., Ohkuma, Y
  • Organizer: RNA 2006 Izu "Functional RNAs and Regulatory Machinery"
  • Place of Presentation: Izunokuni, Japan1
  • Year and Date: 20061200
• [Presentation] A kinase subunit of human Mediator complex CDK8 plays a positive role in transcription (2006)
  • Author(s): Furumoto, T., Tanaka, A., Malik, S., Roeder, R.G., Hanaoka, F., Ohkuma, Y
  • Organizer: 7th EMBL Transcription Meeting
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 20060800
• [Presentation] リン酸化RNAポリメラーゼII-CTD結合蛋白質PCIF1の機能解析 (2006)
  • Author(s): 廣瀬豊, 湯田昌道, 湯の口いずみ, 范紅, 原田文夫, 大熊芳明
  • Organizer: 第8回RNAミーティング
  • Place of Presentation: 淡路島
  • Year and Date: 20060700
• [Presentation] Functional studies of human Mediator subunits (2006)
  • Author(s): Furumoto, T., Ito, M., Roeder, R.G., Hanaoka, F., Ohkuma, Y
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20060600
• [Presentation] The winged helix regions of human TFIIE are essential for transcription of RNA polymerase II (2006)
  • Author(s): Tanaka, A., Watanabe, T., Hanaoka, F., Ohkuma, Y
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20060600
• [Presentation] Functional characterization of the phosphorylated RNA polymerase II interacting factor PCIF1 (2006)
  • Author(s): Hirose, Y., Yuda, M., Yunokuchi, I., Fan, H., Ho, K., Shuman, S., Harada, F
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20060600
• [Presentation] Two opposed transcriptional roles of human Mediator complexes are supported by distinct subunits (2006)
  • Author(s): Ohkuma, Y
  • Organizer: German Science Foundation
  • Place of Presentation: Munich, Germany
  • Year and Date: 2006-08-31
• [Presentation] 真核生物細胞核内の遺伝子発現ネットワーク:基本転写因子TFIIEは転写のスイッチである (2005)
  • Author(s): 林和洋、田中亜紀、古元義、佐藤-土屋千晶、花岡文雄、大熊芳明
  • Organizer: 第28回日本分子生物学会年会, ワークショップ「蛋白質・核酸の修飾による転写制御を中心とした核内クロストーク」
  • Place of Presentation: 福岡
  • Year and Date: 20051200
• [Presentation] TFIIE induces conformational and functional changes in RNA polymerase II during transcription initiation (2005)
  • Author(s): Hayashi, K., Watanabe, T., Tanaka, A., Furumoto, T., Sato-Tsuchiya, C., Yokoi, M., Hanaoka, F., Ohkuma, Y
  • Organizer: 9th Cold Spring Harbor Meeting on Cancer Cells: mechanisms of eukaryotic transcription
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 20050900
• [Presentation] Functional studies of human Mediator subunit Med18/p28b (2005)
  • Author(s): Furumoto, T., Tanaka, A., Malik, S., Ito, M., Roeder, R.G., Hanaoka, F., Ohkuma, Y
  • Organizer: 9th Cold Spring Harbor Meeting on Cancer Cells: mechanisms of eukaryotic transcription
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 20050900
• [Presentation] Functional elucidations of the subdomains of the small subunit of TFIIE (2005)
  • Author(s): Tanaka, A., Hanaoka, F., Ohkuma, Y
  • Organizer: 9th Cold Spring Harbor Meeting on Cancer Cells: mechanisms of eukaryotic transcription
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 20050900
• [Presentation] Coordinated regulation for gene expression - From the studies of the general transcription factors and the Mediator (2005)
  • Author(s): Ohkuma, Y
  • Organizer: Nagasaki Symposium on the Nuclear System to Decipher Operation Code for Biological Responses
  • Place of Presentation: Nagasaki, Japan
  • Year and Date: 20050200
• [Book] 2章 遺伝情報の保持と伝達:2(編集:田村隆明,山本 雅, 改訂第3版 分子生物学イラストレイテッド) (2009)
  • Author(s): 大熊芳明
  • Total Pages: 35-47
  • Publisher: 羊土社
• [Book] 7章 真核生物の転写の分子機構(編集:菊池 洋, ノーベル賞の生命科学入門RNAが拓く新世界) (2009)
  • Author(s): 大熊芳明
  • Total Pages: 126-147
  • Publisher: 講談社
• [Book] III.RNAのプロセシングと編集:mRNAポリメラーゼII-CTDリン酸化制御による転写とmRNAプロセシングの共役「mRNAプログラム-多様性と非対称の獲得戦略」(編集:稲田利文,大野睦人, 蛋白質・核酸・酵素, 12月号増刊) (2009)
  • Author(s): 廣瀬豊
  • Total Pages: 2080-2085
  • Publisher: 共立出版
• [Book] IV.転写制御にかかわる分子群 第12章 基本転写因子による転写開始の分子機構(編集:加藤茂明, 転写制御の分子生物学-ゲノムデコードに向けて-) (2008)
  • Author(s): 大熊芳明
  • Total Pages: 101-107
  • Publisher: 南山堂
• [Book] 分子細胞生物学辞典 第2版(TFIIE、TFIIH、TFIIK、PC4、プロモータークリアランス) (2008)
  • Author(s): 大熊芳明
  • Publisher: 東京化学同人
• [Book] 転写装置シグナリング、「転写因子による生命現象解明の最前線-クロマチン制御機構・エピジェネティクスと転写因子複合体ネットワークの包括的解明-」(編集:五十嵐和彦,深水昭吉,大熊芳明,山本雅之, 実験医学6月号増刊, 25巻) (2007)
  • Author(s): 大熊芳明
  • Total Pages: 1446-1452
  • Publisher: 羊土社