Chromatin dynamics induced by inflammatory stimulation

• Project/Area Number: 26250041
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: System genome science
• Research Institution: The University of Tokyo
• Principal Investigator: Wada Youichiro 東京大学, アイソトープ総合センター, 教授 (10322033)
• Co-Investigator(Kenkyū-buntansha): 神吉 康晴 東京大学, アイソトープ総合センター, 助教 (00534869) ; 藤井 穂高 大阪大学, 微生物病研究所, 准教授 (30302665) ; 興梠 貴英 自治医科大学, 医学部, 准教授 (40401046)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥40,820,000 (Direct Cost: ¥31,400,000、Indirect Cost: ¥9,420,000); Fiscal Year 2016: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2015: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000); Fiscal Year 2014: ¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
• Keywords: 転写 / RNAポリメレースII / 炎症 / 内皮細胞 / ゲノム解析技術 / クロマチン / 質量分析

Outline of Final Research Achievements

Among vascular diseases, atherosclerosis is one of the most important factors of ischemic heart diseases and cerebrovascular diseases, and elucidation of the mechanism in consistent gene expression regulation of atherogenic proteins. To dissect the adhesion molecule gene regulation, we adopted a model using endothelial cells stimulated inflammatory stimulator, and presence of transcription complexes, which regulate multiple genes at the same time, was suggested. In this research, we performed (i) comprehensive chromatin interaction analysis, (ii) identification of interaction associated proteincomplex, (iii) intervention of chromatin structure, and it was observed that transcription factories regulated both induced and reduced genes from different chromosomes.

Research Products

• [Int'l Joint Research] Oxford University(England)
• [Int'l Joint Research] University of Connecticut/Harvard University(United States)
• [Int'l Joint Research] Shandong Univeristy/Huazhong Agricultural University(China)
• [Int'l Joint Research] Oxford University(England)
• [Int'l Joint Research] University of Connecticut/Harvard University(United States)
• [Int'l Joint Research] Shandong University(China)
• [Journal Article] Dynamically and epigenetically coordinated GATA/ETS/SOX transcription factor expression is indispensable for endothelial cell differentiation. (2018)
  • Author(s): Kanki Y, Nakaki R, Shimamura T, Matsunaga T, Yamamizu K, Katayama S, Suehiro JI, Osawa T, Aburatani H, Kodama T, Wada Y, Yamashita JK, Minami T.
  • Journal Title: Nucleic Acids Res. Volume: 印刷中 Pages: 4344-4358
  • DOI: 10.1093/nar/gkx159
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Role of Cdkn1A-Interacting Zinc Finger Protein 1 (CIZ1) in DNA Replication and Pathophysiology. (2016)
  • Author(s): Liu Q, Niu N, Wada Y, Liu J.
  • Journal Title: Int J Mol Sci. Volume: 17
  • DOI: 10.3390/ijms17020212
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells (2016)
  • Author(s): Katsura M, Cyou-Nakamine H, Zen Q, Zen Y, Nansai H, Amagasa S, Kanki Y, Inoue T, Kaneki K, Taguchi A, Kobayashi M, Kaji T, Kodama T, Miyagawa K, Wada Y, Akimitsu N, Sone H.
  • Journal Title: Scientific Reort Volume: 6 Pages: 20027-20027
  • DOI: 10.1038/srep20027
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Low-Dose Cadmium Upregulates VEGF Expression in Lung Adenocarcinoma Cells. (2015)
  • Author(s): Liu F, Wang B, Li L, Dong F, Chen X, Li Y, Dong X, Wada Y, Kapron CM, Liu J.
  • Journal Title: Int J Environ Res Public Health Volume: 12 Pages: 10508-21
  • DOI: 10.3390/ijerph120910508
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct effects of Hoxa2 overexpression in cranial neural crest populations reveal that the mammalian hyomandibular-ceratohyal boundary maps within the styloid process. (2015)
  • Author(s): Kitazawa T, Fujisawa K, Narboux-Nême N, ArimA Y, Kawamura Y, Inoue T, Wada Y, Kohro T, Aburatani H, Kodama T, Kim K-S, Sato T, Uchijima Y, Maeda K, Miyagawa-Tomita S, Minoux M, Rijli FM, Levi G, Kurihara Y, Kurihara H.
  • Journal Title: Dev Biol Volume: 402 Pages: 162-174
  • DOI: 10.1016/j.ydbio.2015.04.007
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Direct evidence for pitavastatin induced chromatin structure change in the KLF4 gene in endothelial cells (2015)
  • 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
  • DOI: 10.1371/journal.pone.0096005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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 Biol. Volume: 15
  • DOI: 10.1186/gb-2014-15-4-r63
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Dynamics of chromatin structure in stimulated vascular endothelial cells (2016)
  • Author(s): 和田洋一郎
  • Organizer: 第54回日本生物物理学会年会
  • Place of Presentation: つくば会議場（茨城県つくば市）
  • Year and Date: 2016-11-25
  • Invited
• [Presentation] Dynamic chromatin movement in stimulated endothelial cells suggested by interactome analysis (2016)
  • Author(s): 和田洋一郎
  • Organizer: 3D nucleome workshop
  • Place of Presentation: Huazhong Agricultural University, Wuhan, China
  • Year and Date: 2016-09-24
  • Int'l Joint Research / Invited
• [Presentation] 炎症刺激におけるクロマチン構造変化を介した 遺伝子発現の制御機構 (2016)
  • Author(s): 和田洋一郎
  • Organizer: 第17回日本分子脳神経外科学会
  • Place of Presentation: 帝京大学板橋キャンパス本部棟（東京都板橋区）
  • Year and Date: 2016-08-26
  • Invited
• [Presentation] Dynamic chromatin movement in stimulated endothelial cells suggested by interactome analysis (2015)
  • Author(s): 和田洋一郎
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-12-02
  • Int'l Joint Research / Invited