Runx-mediated regulation of chemokine CCL5 for lung diseases

• Project/Area Number: 15K08535
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Seo Wooseok 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (40574116)
• Project Period (FY): 2015-10-21 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: アレルギー / 免疫関連疾患 / 免疫関連病患

Outline of Final Research Achievements

CCL5 chemokine is related to the development of many inflammatory diseases. To understand how CCL5 is regulated, I have examined a knockout mouse of Runx/CBFβ transcription factor and discovered that CCL5 is hugely upregulated in the absence of Runx/CBFβ. This indicated that CCL5 is tightly regulated by Runx/CBFβ. By combining regular ChIP and novel enChIP assays, I discovered that CCL5 expression requires two separate enhancers depending on activation states. These enhancers are crucial for proper expression of CCL5 from T cells as well as T-cell immunity.

Research Products

• [Journal Article] Essential Roles of SATB1 in Specifying T Lymphocyte Subsets (2017)
  • Author(s): Kakugawa Kiyokazu、Kojo Satoshi、Tanaka Hirokazu、Seo Wooseok、Endo Takaho A.、Kitagawa Yohko、Muroi Sawako、Tenno Mari、Yasmin Nighat、Kohwi Yoshinori、Sakaguchi Shimon、Kowhi-Shigematsu Terumi、Taniuchi Ichiro
  • Journal Title: Cell Rep Volume: 19 Issue: 6 Pages: 1176-1188
  • DOI: 10.1016/j.celrep.2017.04.038
  • NAID: 40021496454
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes. (2017)
  • Author(s): Kojo S, Tanaka H, Endo TA, Muroi S, Liu Y, Seo W, Tenno M, Kakugawa K, Naoe Y, Nair K, Moro K, Katsuragi Y, Kanai A, Inaba T, Egawa T, Venkatesh B, Minoda A, Kominami R, Taniuchi I.
  • Journal Title: Nat Commun. Volume: 8 Issue: 1 Pages: 702-702
  • DOI: 10.1038/s41467-017-00768-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct requirement of Runx complexes for TCRβ enhancer activation at distinct developmental stages. (2017)
  • Author(s): Seo W, Muroi S, Akiyama K and Taniuchi I.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 41351-41351
  • DOI: 10.1038/srep41351
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Regulation of hematopoiesis and immune responses by long noncoding RNAs. (2017)
  • Author(s): Seo W. and Taniuchi I.
  • Journal Title: International Immunology Volume: 印刷中 Issue: 4 Pages: 165-172
  • DOI: 10.1093/intimm/dxx021
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Roles of RUNX Complexes in Immune Cell Development (2017)
  • Author(s): Ebihara T., Seo W., Taniuchi I.
  • Journal Title: Advances in Experimental Medicine and Biology Volume: 962 Pages: 395-413
  • DOI: 10.1007/978-981-10-3233-2_24
  • ISBN: 9789811032318, 9789811032332
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Transcriptional regulation of early T-cell development in the thymus. (2016)
  • Author(s): Seo W, Taniuchi I
  • Journal Title: Eur J Immunol. Volume: 46 Issue: 3 Pages: 531-8
  • DOI: 10.1002/eji.201545821
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Regulation of CCL5 expression by Runx complexes and two stage-specific enhancers (2017)
  • Author(s): Wooseok Seo, Kosuke Miyauchi, Masato Kubo and Ichiro Taniuchi
  • Organizer: 日本免疫学会
• [Presentation] Regulation of thymocyte fate decision by local chromatin structure (2016)
  • Author(s): Seo W. and Taniuchi I.
  • Organizer: Japanese Society of Immunology
  • Place of Presentation: Okinawa (Japan)
  • Year and Date: 2016-12-05
• [Presentation] Regulation of CCL5 by Runx/CBFβ is essential to maintain lung homeostasis (2016)
  • Author(s): Seo W. and Taniuchi I.
  • Organizer: International Congress of Immunology
  • Place of Presentation: Melbourne (Australia)
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Control of thymocyte fate decision by local chromatin structure (2015)
  • Author(s): Wooseok Seo
  • Organizer: 2015 Annual Meeting of Molecular Biology Society of Japan
  • Place of Presentation: Kobe International Convention Center, Kobe, Hyogo
  • Year and Date: 2015-12-04
  • Invited
• [Presentation] Repression of CCL5 by Runx/CBFβ is essential to prevent lung infiltration (2015)
  • Author(s): Wooseok Seo
  • Organizer: 2015 Annual Meeting of Japanese Society of Immunlogy
  • Place of Presentation: Sapporo Convention Center, Sapporo, Hokkaido
  • Year and Date: 2015-11-18