Structural Basis for the chromatin remodeling by nuclear receptors

2013 Fiscal Year Final Research Report

• 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
• 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 Pages: 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): Manami Hashimoto, Noriyuki Kodera, Yasuo Tsunaka, Masayuki Oda, Mitsuru Tanimoto, Toshio Ando, Kosuke Morikawa, & Shin-ichi Tate
  • Journal Title: Biophysical J. Volume: 104 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
• [Journal Article] Design and synthesis of a series of α-benzyl phenylpropanoic acid-type peroxisome proliferator-activated receptor (PPAR) gamma partial agonists with improved aqueous solubility (2013)
  • Author(s): Masao Ohashi, Takuji Oyama, Endy Widya Putranto, Tsuyoshi Waku, Hiromi Nobusada, Ken Kataoka, Kenji Matsuno, Masakazu Yashiro, Kosuke Morikawa, Nam-ho Huh, & Hiroyuki Miyachi
  • Journal Title: Bioorg. Med. Chem. Volume: 21 Pages: 2319-2332
  • DOI: 10.1016/j.bmc.2013.02.003
  • Peer Reviewed
• [Journal Article] CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold (2012)
  • Author(s): Tatsuya Nishino, Kozo Takeuchi, Karen E Gascoigne, Aussie Suzuki, Tetsuya Hori, Takuji Oyama, Kosuke Morikawa, Iain M Cheeseman, & Tatsuo Fukagawa
  • Journal Title: Cell. Volume: 148 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): Maiko Tanabe, Sonoko Ishino, Masafumi Yohda, Kosuke Morikawa, Yoshizumi Ishino, & Hirokazu Nishida
  • Journal Title: Chembiochem. Volume: 13 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, Takuji Oyama, Jun Ichi Kasuga, Kenji Ohgane, Yoshino Nishio, Kosuke Morikawa, Yuichi Hashimoto, & Hiroyuki Miyachi
  • Journal Title: Bioorg. Med. Chem. Volume: 20 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): Aussie Suzuki, Tetsuya Hori, Tatsuya Nishino, Jiro Usukura, Atsushi Miyagi, Kosuke Morikawa, & Tatsuo Fukagawa
  • Journal Title: J Cell Biol. Volume: 193 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 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 Pages: 397-403
  • DOI: 10.1093/protein/gzq121
  • 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] 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] 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