ChIP-seq analysis of transcriptional regulation by BMP in relation to pulmonary hypertension

• Project/Area Number: 22790750
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: KOINUMA Daizo 東京大学, 大学院・医学系研究科, 講師 (80375071)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シグナル伝達 / ゲノム / 内科 / 病理学 / 循環器・高血圧

Research Abstract

Bone morphogenetic protein(BMP) signaling is closely related to idiopathic pulmonary hypertension. Using pulmonary arterial smooth muscle cells(PASMCs) and endothelial cells, we determined Smad1/Smad5 binding sites by chromatin immunoprecipitation-sequencing(ChIP-seq). We identified PASMCs-specific novel target gene. We examined and found its role in patho-physiology of pulmonary hypertension by siRNA and its inhibitor.

Research Products

• [Journal Article] Genome-wide mechanisms of Smad binding (2013)
  • Author(s): Morikawa M
  • Journal Title: Oncogene Volume: 32 Issue: 13 Pages: 1609-1615
  • DOI: 10.1038/onc.2012.191
  • Peer Reviewed
• [Journal Article] Tumor-promoting functions of transforming growth factor-βin progression of cancer (2012)
  • Author(s): Miyazono K, Ehata S, Koinuma D
  • Journal Title: Ups J Med Sci Volume: 117(2) Pages: 143-152
  • Peer Reviewed
• [Journal Article] TGF-β-induced epithelial-mesenchymal transition of A549 lung adenocarcinoma cells is enhanced by pro-inflammatory cytokines derived from RAW 264. 7 macrophage cells (2012)
  • Author(s): Kawata M, Koinuma D, Ogami T, Umezawa K, Iwata C, Watabe T, and Miyazono K.
  • Journal Title: J Biochem Volume: 151(2) Pages: 205-216
  • Peer Reviewed
• [Journal Article] TGF-β derives epithelial-mesenchymal transition through δEF1-mediated downregulation of ESRP (2011)
  • Author(s): 堀口華奈
  • Journal Title: Oncogene Volume: (掲載確定)(印刷中) Issue: 26 Pages: 3190-3201
  • DOI: 10.1038/onc.2011.493
  • Peer Reviewed
• [Journal Article] RB1CC1 protein positivelyregulates transforming growth factor-beta signaling through the modulation of Arkadia E3 ubiquitin ligase activity (2011)
  • Author(s): Koinuma D, Shinozaki M, Nagano Y, Ikushima H, Horiguchi K, Goto K, Chano T, Saitoh M, Imamura T, Miyazono K, and Miyazawa K.
  • Journal Title: J Biol Chem Volume: 286(37) Pages: 32502-32512
  • Peer Reviewed
• [Journal Article] ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif (2011)
  • Author(s): Morikawa M, Koinuma D, Tsutsumi S, Vasilaki E, Kanki Y, Heldin CH, Aburatani H, Miyazono K.
  • Journal Title: Nucleic Acids Res Volume: 39(20) Pages: 8712-8727
  • Peer Reviewed
• [Journal Article] Cell type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4 alpha in HepG2 cells (2011)
  • Author(s): Mizutani A, Koinuma D, Tsutsumi S, Kamimura N, Morikawa M, Suzuki HI, Imamura T, Miyazono K, Aburatani H.
  • Journal Title: J Biol Chem Volume: 286(34) Pages: 29848-29860
  • Peer Reviewed
• [Journal Article] ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif (2011)
  • Author(s): Morikawa M, Koinuma D, Tsutsumi S,Vasilaki E, Kanki Y, Heldin CH, Aburatani H, Miyazono K
  • Journal Title: Nucleic Acids Res Volume: 39(20) Issue: 20 Pages: 8712-27
  • DOI: 10.1093/nar/gkr572
  • Peer Reviewed
• [Journal Article] TGF-βによる転写制御 (2010)
  • Author(s): 鯉沼代造
  • Journal Title: 医学のあゆみ Volume: 234 Pages: 900-905
• [Presentation] 次世代シーケンサーが明らかにするTGF-βファミリーシグナルの転写制御機構 (2012)
  • Author(s): 鯉沼代造
  • Organizer: 第27回つくば分子病理学セミナー
  • Place of Presentation: 筑波大学(茨城県)(招待講演)
  • Year and Date: 2012-02-08
• [Presentation] Change in alternative splicing of FGFR during TGF-β-induced EMT. The 1st International Symposium by JSPS Core-to-Core Program (2012)
  • Author(s): Horiguchi K, Koinuma D, Semba K, Miyazawa K, Miyazono K, Saitoh M.
  • Organizer: Cooperative International Framework in TGF-βFamily Signaling
  • Place of Presentation: 東京大学小柴ホール(東京都)
  • Year and Date: 2012-01-23
• [Presentation] Inhibitory mechanism of Thyroid transcription factor-1 on TGF-βsignaling in lung cancer cells. The 1st International Symposium by JSPS Core-to-Core Program (2012)
  • Author(s): Isogaya K, Koinuma D, Tsutsumi S, Saito RA, Miyazawa K, Aburatani H, Miyazono K.
  • Organizer: Cooperative International Framework in TGF-βFamily Signaling
  • Place of Presentation: 東京大学小柴ホール(東京都)
• [Presentation] Mechanism of Smad Signaling Modification by TTF1 in lung Cancer Cells (2011)
  • Author(s): Isogaya K, Koinuma D, Tsutsumi S, Saito RA, Aburatani H, Miyazono K
  • Organizer: UCSF, 36th Annual Tetrad Research Conference
  • Place of Presentation: Lake Tahoe, U. S. A.
• [Presentation] ChIP-seq reveals cell-type specific binding patterns of BMP-specific Smads and a novel binding motif (2011)
  • Author(s): Morikawa M, Koinuma D, Tsutsumi S, Vasilaki E, Kanki Y, Heldin CH, Aburatani H, Miyazono K.
  • Organizer: FASEB Summer Research Conferences on the TGF-βSuperfamily
  • Place of Presentation: Lucca, Italy
• [Presentation] "Cistrome" of the TGF-β-Smad signaling pathway (2010)
  • Author(s): 鯉沼代造
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
  • Place of Presentation: ポートピアホテル(兵庫県 神戸市)
  • Year and Date: 2010-12-10
• [Presentation] Characterization of Smad2 and Smad3 binding sites by genome-wide ChIP-chip/ChIP-sequencing analysis (2010)
  • Author(s): 鯉沼代造
  • Organizer: 藤原セミナー
  • Place of Presentation: グランドホテルニュー王子(北海道 苫小牧市)
  • Year and Date: 2010-07-16