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

2011 Fiscal Year Final Research Report

• 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
• 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 (2012)
  • Author(s): Morikawa M, Koinuma D, Miyazono K, and Heldin, C-H.
  • Journal Title: Oncogene
  • DOI: 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-βdrives epithelial-mesenchymal transition throughδEF1-mediated downregulation of ESRP (2012)
  • Author(s): Horiguchi K, Sakamoto K, Koinuma D, Semba K, Inoue A, Inoue S, Fujii H, Yamaguchi A, Miyazawa K, Miyazono K, and Saitoh M.
  • Journal Title: Oncogene
  • DOI: 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
• [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)
  • Year and Date: 20120123-24
• [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] 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.
  • Year and Date: 20110908-10
• [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
  • Year and Date: 20110821-26