Identification of PPARdelta transcriptional complex by photo-crosslinking

• Project/Area Number: 25670035
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: TANAKA Toshiya 東京大学, 先端科学技術研究センター, 特任准教授 (20396930)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 核内受容体 / プロテオミクス / クロスリンク / PPARδ

Outline of Final Research Achievements

We have carried out to establish a transcription factor complex identification method combining cross-linking and high-resolution mass spectrometry using PPARδ as a model transcription factor.
We found photo-reactive amino acids induce cell toxicity. Formaldehyde cross-linking causes decrease in coverage of target protein and increase in non-specific protein binding. Knockdown of SATB1, which is identified as macrophage-specific PPARδ interact protein, by shRNA reduces macrophage-specific PPARδ target gene induction by PPARδ agonist.
These results suggest the possibility of the identification of native PPARδ transcriptional complex using combination of cross-linking and high-resolution mass spectrometry.

Research Products

• [Journal Article] The FBXL10/KDM2B Scaffolding Protein Associates with Novel Polycomb Repressive Complex-1 to Regulate Adipogenesis. (2015)
  • Author(s): Inagaki T, Iwasaki S, Matsumura Y, Kawamura T, Tanaka T, Abe Y, Yamasaki A, Tsurutani Y, Yoshida A, Chikaoka Y, Nakamura K, Magoori K, Nakaki R, Osborne TF, Fukami K, Aburatani H, Kodama T, Sakai J
  • Journal Title: J Biol Chem Volume: 290 Issue: 7 Pages: 4163-77
  • DOI: 10.1074/jbc.m114.626929
  • Peer Reviewed / Open Access
• [Journal Article] Transcriptome Analysis of K-877 (a Novel Selective PPARα Modulator (2015)
  • Author(s): S Raza-Iqbal, T Tanaka, M Anai, T Inagaki, Y Matsumura, K Ikeda, A Taguchi, FJ. Gonzalez, J Sakai, Kodama
  • Journal Title: J Atheroscler Thromb Volume: 22
  • Peer Reviewed / Open Access
• [Journal Article] JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis (2015)
  • Author(s): Y Abe, R Rozqie, Y Matsumura, T Kawamura, R Nakaki, Y Tsurutani, K Tanimura-Inagaki, A Shiono, K Magoori, K Nakamura, S Ogi, S Kajimura, H Kimura, T Tanaka, K Fukami, T Osborne, T Kodama, H Aburatani, T Inagaki, J Sakai
  • Journal Title: Nature Commun Volume: 6
  • Peer Reviewed / Open Access
• [Journal Article] Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements. (2014)
  • Author(s): Inoue T, Kohro T, Tanaka T, Kanki Y, Li G, Poh HM, Mimura I, Kobayashi M, Taguchi A, Maejima T, Suehiro JI, Sugiyama A, Kaneki K, Aruga H, Dong S, Stevens JF, Yamamoto S, Tsutsumi S, Fujita T, Ruan X, Aburatani H, Nangaku M, Ruan Y, Kodama T, Wada Y.
  • Journal Title: Genome Biology Volume: 15 Issue: 4
  • DOI: 10.1186/gb-2014-15-4-r63
  • Peer Reviewed / Open Access
• [Journal Article] Direct Evidence for Pitavastatin Induced Chromatin Structure Change in the KLF4 Gene in Endothelial Cells. (2014)
  • Author(s): Maejima T, Inoue T, Kanki Y, Kohro T, Li G, Ohta Y, Kimura H, Kobayashi M, Taguchi A, Tsutsumi S, Iwanari H, Yamamoto S, Aruga H, Dong S, Stevens JF, Poh HM, Yamamoto K, Kawamura T, Mimura I,
  • Journal Title: PLoS One. Volume: 9 Issue: 5 Pages: e96005-e96005
  • DOI: 10.1371/journal.pone.0096005
  • Peer Reviewed / Open Access
• [Journal Article] PPARβ/δ activation of CD300a controls intestinal immunity. (2014)
  • Author(s): Tanaka T, Tahara-Hanaoka S, Nabekura T, Ikeda K, Jiang S, Tsutsumi S, Inagaki T, Magoori K, Higurashi T, Takahashi H, Tachibana K, Tsurutani Y, Raza S, Anai M, Minami T, Wada Y, Yokote K, Doi T, Hamakubo T, Auwerx J, Gonzalez FJ, Nakajima A, Aburatani H, Naito M, Shibuya A, Kodama T, Sakai J.
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 5412-5412
  • DOI: 10.1038/srep05412
  • Peer Reviewed / Open Access
• [Presentation] FBXL10によるエピゲノム複合体を介した脂肪細胞分化調節機構 (2014)
  • Author(s): 稲垣毅，岩崎聡，松村欣宏，川村猛，阿部陽平，吉田文乃，中村加奈子，馬郡健太，仲木竜，田中十志也，児玉龍彦，油谷浩幸，酒井寿郎
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県、横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] PPARβ/δはCD300aの活性化を介して腸管免疫を制御する (2014)
  • Author(s): 田中十志也，田原聡子，Jiang Shuing，内藤眞，渋谷彰，児玉龍彦，酒井寿郎
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県、横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] JMJD1Aのリン酸化スイッチはクロマチンリモデリング因子およびPPARγと複合体を形成し、クロマチンの高次構造を変化させる (2014)
  • Author(s): 阿部陽平，Royhan Rozqie，松村欣宏，川村猛，仲木竜，鶴谷悠也，稲垣（谷村）恭子，塩野陽，馬郡健太，田中十志也，児玉龍彦，油谷浩幸，稲垣毅，酒井寿郎
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県、横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] PPARβ/δはCD300aの活性化を介して腸管免疫を制御する (2014)
  • Author(s): 田中十志也
  • Organizer: 第22回ステロイドホルモン学会学術集会
  • Place of Presentation: 都道府県会館（東京都、千代田区）
  • Year and Date: 2014-11-03