Structural Basis for the chromatin remodeling by nuclear receptors

• Project/Area Number: 23247016
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: International Institute for Advanced Studies
• Principal Investigator: MORIKAWA Kosuke 公益財団法人国際高等研究所, チーフリサーチフェロー (80012665)
• Co-Investigator(Renkei-kenkyūsha): TSUNAKA Yasuo 京都大学, 物質-細胞統合システム拠点, 特任講師 (40551552) ; FUKAGAWA Tatsuo 国立遺伝学研究所, 分子遺伝研究系, 教授 (60321600) ; ANDO Toshio 金沢大学, 数物科学系, 教授 (50184320) ; MAYANAGI Kota 九州大学, 生体防御医学研究所, 助教 (50418571)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥48,490,000 (Direct Cost: ¥37,300,000、Indirect Cost: ¥11,190,000); Fiscal Year 2013: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000); Fiscal Year 2012: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000); Fiscal Year 2011: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
• Keywords: 核内受容体 / クロマチン / 構造生物学 / 発現制御

Research Abstract

Nuclear receptors belong to a class of transcription factors that function at the initial stage of gene regulation mechanisms, in response to environmental changes. We studied the interaction of nuclear receptors with in-vitro reconstituted nucleosomes by biochemical experiments. We found that the nucleosome functions as a barrier and prevents the specific binding of nuclear receptors to DNA. These results suggest that the chromatin remodeling should be the prerequisite for the docking of nuclear receptors onto the target DNA sequence in the genome.

Research Products

• [Journal Article] Mutational and Structural Analyses of Caldanaerobius polysaccharolyticus Man5B Reveal Novel Active Site Residues for Family 5 Glycoside Hydrolases (2013)
  • Author(s): Takuji Oyama, George E Schmitz, Dylan Dodd, Yejun Han, Alanna Burnett, Naoko Nagasawa, Roderick I Mackie, Haruki Nakamura, Kosuke Morikawa, & Isaac Cann
  • Journal Title: PLoS ONE. Volume: 8 Issue: 11 Pages: e80448-e80448
  • DOI: 10.1371/journal.pone.0080448
  • Peer Reviewed
• [Journal Article] Phosphorylation-coupled Intramolecular Dynamics of Unstructured Regions in Chromatin Remodeler FACT (2013)
  • Author(s): M.Hashimoto, N.Kodera, Y.Tsunaka, M.Oda, M.Tanimoto, T.Ando, K.Morikawa, and S.Tate
  • Journal Title: Biophys. J. Volume: 104 Issue: 10 Pages: 2222-2234
  • DOI: 10.1016/j.bpj.2013.04.007
  • Peer Reviewed
• [Journal Article] 生体内代謝をモニターする転写システム : 核内受容体 PPARγによる転写を介した代謝ネットワーク間のクロストーク (2013)
  • Author(s): 白木拓磨, 和久剛, 森川耿右
  • Journal Title: 生化学 Volume: 第85巻 Pages: 749-761
  • NAID: 10031202187
• [Journal Article] Design and synthesis of a series of a-benzyl phenylpropanoic acid-type peroxisome proliferator-activated receptor (PPAR) gamma partial agonists with improved a queous solubility. (2013)
  • Author(s): Masao Ohashi, et.al.
  • Journal Title: Bioorg. Med Chem. Volume: 21 Issue: 8 Pages: 2319-2332
  • DOI: 10.1016/j.bmc.2013.02.003
  • Peer Reviewed
• [Journal Article] 生体内代謝をモニターする転写システム：核内受容体PPARγによる転写を介した代謝ネットワーク間のクロストーク (2013)
  • Author(s): 白木 拓磨, 和久 剛, 森川 耿右
  • Journal Title: 生化学 Volume: 85 Pages: 749-761
  • NAID: 10031202187
• [Journal Article] "CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold." (2012)
  • Author(s): Nishino T, Takeuchi K, Gascoigne, KT, Suzuki A, Hori T, Oyama T, Morikawa K, Cheeseman IM, Fukagawa T
  • Journal Title: Cell Volume: 148 Issue: 3 Pages: 487-501
  • DOI: 10.1016/j.cell.2011.11.061
  • Peer Reviewed
• [Journal Article] Structure-based mutational study of an archaeal DNA ligase towards improvement of ligation activity. (2012)
  • Author(s): Tanabe, M.
  • Journal Title: ChemBioChem. Volume: 13 Issue: 17 Pages: 2575-2582
  • DOI: 10.1002/cbic.201200336
  • Peer Reviewed
• [Journal Article] Bidirectional fluorescence properties of pyrene-based peroxisome proliferator-activated receptor (PPAR) α/δ dual agonist. (2012)
  • Author(s): Shintaro Ban 他７名
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 20 Issue: 11 Pages: 3460-3464
  • DOI: 10.1016/j.bmc.2012.04.015
  • Peer Reviewed
• [Journal Article] "Spindle microtubules generate tension-dependent changes in the distribution of inner kinetochore proteins." (2011)
  • Author(s): Suzuki A, Hori T, Nishino T, Usukura J, Miyagi A, Morikawa K, Fukagawa T
  • Journal Title: J. Cell Biol Volume: 193 Issue: 1 Pages: 125-140
  • DOI: 10.1083/jcb.201012050
  • Peer Reviewed
• [Journal Article] Architectures of archaeal GINS complexes, essential DNA replication initiation factors (2011)
  • Author(s): Takuji Oyama, Sonoko Ishino, Seiji Fujino, Hiromi Ogino, Tsuyoshi Shirai, Kouta Mayanagi, Mihoko Saito, Naoko Nagasawa, Yoshizumi Ishino, & Kosuke Morikawa
  • Journal Title: BMC Biol. Volume: 9 Issue: 1 Pages: 1-17
  • DOI: 10.1006/jsbi.1999.4174
  • Peer Reviewed
• [Journal Article] Detecting structural similarity of ligand interactions in the lipid metabolic system including enzymes, lipid-binding proteins and nuclear receptors (2011)
  • Author(s): Clara Shionyu-Mitsuyama, Tsuyoshi Waku, Takuma Shiraki, Takuji Oyama, Tsuyoshi Shirai, & Kosuke Morikawa
  • Journal Title: Protein Eng Des Sel. Volume: 24 Issue: 4 Pages: 397-403
  • DOI: 10.1093/protein/gzq121
  • Peer Reviewed
• [Journal Article] Architectures of archaeal GINS complexes, essential DNA replication initiation factors (2011)
  • Author(s): Oyama, T., et al
  • Journal Title: BMC Biology Volume: 9 Issue: 1 Pages: 28-28
  • DOI: 10.1186/1741-7007-9-28
  • Peer Reviewed
• [Presentation] Structural basis for the activation of the nuclear receptor, PPARgamma, by fatty acid-and serotonin metabolites (2012)
  • Author(s): 和久剛、白木琢磨、大山拓次、塩生くらら、森川耿右
  • Organizer: 第85回日本生化学大会
  • Place of Presentation: 福岡国際会議場マリンメッセ福岡
  • Year and Date: 2012-12-15
  • Invited
• [Presentation] in-cell NMRを用いた脂肪酸結合タンパク質FABP4の機能解析 (2011)
  • Author(s): 森戸昭等、猪股晃介、森川耿右、杤尾豪人、白川昌宏
  • Organizer: 第34回日本分子生物学会年会トーク
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-14
• [Presentation] 核内受容体PPARγリガンド結合ドメインと含窒素6員環を持つPPARγ特異的アゴニストの複合体結晶構造 (2011)
  • Author(s): 大山拓次、和久剛、大橋雅生、宮地弘幸、森川耿右
  • Organizer: 第34回日本分子生物学会年会ポスター
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-14
• [Presentation] 核内受容体 PPARγの機能解析 : 分子生物学的アプローチと生化学的アプローチ (2011)
  • Author(s): 白木拓磨、五十嵐和彦、森川耿右
  • Organizer: 第84回日本生化学会大会シンポジウム
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2011-09-23
  • Invited
• [Presentation] 核内受容体PPARγの機能解析:分子生物学的アプローチと生化学的アプローチ (2011)
  • Author(s): 白木琢磨、五十嵐和彦、森川耿右
  • Organizer: 第84回日本生化学会大会シンポジウム
  • Place of Presentation: 国立京都国際会館(招待講演)
  • Year and Date: 2011-09-23
• [Presentation] 単粒子解析によるDNA複製の制御機構の研究 (2011)
  • Author(s): 真柳浩太、清成信一、西田洋一、齊藤美保子、神田大輔、石野良純、白井剛、森川耿右
  • Organizer: 第11回日本蛋白質科学会年会ポスター
  • Place of Presentation: ホテル阪急エキスポパーク
  • Year and Date: 2011-06-09
• [Presentation] 核内受容体PPARγリガンド結合ドメインと新規PPARγ特異的アゴニストの複合体結晶構造 (2011)
  • Author(s): 大山拓次、和久剛、大橋雅生、宮地弘幸、森川耿右
  • Organizer: 第11回日本蛋白質科学会年会ポスター
  • Place of Presentation: ホテル阪急エキスポパーク
  • Year and Date: 2011-06-09
• [Presentation] 脊椎動物動原体構成因子CENP-S/X、CENP-T/W複合体の構造細胞生化学と溶液動態解析 (2011)
  • Author(s): 西野達哉、鈴木應志、竹内康造、堀哲也、宮城篤、大山拓次、森川耿右、深川竜郎
  • Organizer: 第11回日本蛋白質科学会年会ポスター
  • Place of Presentation: ホテル阪急エキスポパーク
  • Year and Date: 2011-06-08
• [Presentation] 脂質結合系のタンパク質構造の共進化 (2011)
  • Author(s): 塩生くらら、和久剛、白木琢磨、大山拓次、白井剛、森川耿右
  • Organizer: 第11回日本蛋白質科学会ワークショップ
  • Place of Presentation: ホテル阪急エキスポパーク
  • Year and Date: 2011-06-07
  • Invited
• [Presentation] 脂質結合系のタンパク質構造の共進化 (2011)
  • Author(s): 塩生くらら、和久剛, 白木琢磨、大山拓次, 白井剛、森川耿右
  • Organizer: 第11回日本蛋白質科学会年会ワークショップ
  • Place of Presentation: ホテル阪急エキスポパーク(招待講演)
  • Year and Date: 2011-06-07
• [Presentation] Structural basis for the activation of the nuclear receptor, PPARgamma, by fatty acid-and serotonin metabolites.
  • Author(s): Waku, T., Shiraki, T., Oyama, T., Shionyu, C. & Morikawa, K.
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡、福岡
  • Invited
• [Presentation] The Synergistic Stimulation of the MCM Activity by Cdc6/Orc1 and GINS Homotetramer from the Archaeon,Thermoplasma Acidophilum.
  • Author(s): 2. Ogino, H., Ishino, S., Mayanagi, K., Oyama, T., Shiraki, T., Morikawa, K., Haugland, G. T., Birkeland, N-K. & Ishino, Y.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡、福岡