Comprehensive analysis of gene expression regulation during mononuclear phagocyte development
| Project/Area Number |
15H04860
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中林 潤 横浜市立大学, 先端医科学研究センター, 准教授 (80322733)
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| Co-Investigator(Renkei-kenkyūsha) |
KUROTAKI Daisuke 横浜市立大学, 医学部, 講師 (10568455)
NISHIYAMA Akira 横浜市立大学, 医学部, 准教授 (80589664)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
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| Keywords | エンハンサー / 単球 / 樹状細胞 / 転写因子 / ChIP-seq / 血球細胞分化 / 遺伝子発現制御 / 細胞分化 / 発生・分化 / 遺伝子 / 発現制御 / 単核貪食細胞分化 |
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| Outline of Final Research Achievements |
Monocytes and dendritic cells (DCs), called mononuclear phagocytes, are critical for host defense and tissue homeostasis. These cells develop from bone marrow hematopoietic stem cells via intermediate progenitors. However, molecular mechanisms underlying the regulation of gene expression during monocyte and DC development still remain obscure. In this research project, we analyzed the genome-wide dynamics of enhancer landscape, gene expression, and chromatin binding of key transcription factors in various differentiation stages of myeloid cells. We found that the chromatin binding of IRF8, which recruits binding of PU.1, induces the formation of monocyte and DC-specific enhancers in the progenitor stages, leading to the future expression of genes that confer the characteristics of mononuclear phagocytes. These results contribute to a comprehensive understanding of how transcription factors affect chromatin to regulate gene expression during cell differentiation.
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Report
(3 results)
Research Products
(42 results)
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[Journal Article] Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity.2016
Author(s)
Ban T., Sato G.R., Nishiyama A., Akiyama A., Takasuna M., Umehara M., Suzuki S., Ichino M., Matsunaga S., Kimura A., Kimura Y., Yanai H., Miyashita S., Kuromitsu J., Tsukahara K., Yoshimatsu K., Endo I., Yamamoto T., Hirano H., Ryo A., Taniguchi T., Tamura T.
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Journal Title
Immunity
Volume: 45
Issue: 2
Pages: 319-332
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Enhancer Landscape Dynamics and the Role of IRF8 in Mononuclear Phagocyte Development2015
Author(s)
Kurotaki D, Nakabayashi J, Nishiyama A, Sasaki H, Kaneko N, Koizumi S, Ozato K, Suzuki Y, Tamura T
Organizer
57th American Society of Hematology Annual Meeting and Exposition
Place of Presentation
Orange County Convention Center, Orlando, FL, USA
Year and Date
2015-12-06
Related Report
Int'l Joint Research
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[Presentation] A role of the transcription factor IRF8 in basophil and mast cell development2015
Author(s)
Sasaki H, Kurotaki D, Osato N, Sato H, Sasaki I, Koizumi S, Wang H, Kaneda C, Nishiyama A, Kaisho T, Aburatani H, Morse HC III, Ozato K, Tamura T
Organizer
International Society for Experimental Hematology 44th Annual Scientific Meeting
Place of Presentation
国立京都国際会館（京都府京都市）
Year and Date
2015-09-18
Related Report
Int'l Joint Research
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[Presentation] IRF8 inhibits the activity of C/EBPα to restrain mononuclear phagocyte progenitors from differentiating into neutrophils2015
Author(s)
Kurotaki D, Yamamoto M, Nishiyama A, Uno K, Ban T, Ichino M, Sasaki H, Matsunaga S, Yoshinari M, Ryo A, Nakazawa M, Ozato K, Tamura T
Organizer
International Society for Experimental Hematology 44th Annual Scientific Meeting
Place of Presentation
国立京都国際会館（京都府京都市）
Year and Date
2015-09-17
Related Report
Int'l Joint Research
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[Presentation] 好塩基球、マスト細胞分化における転写因子IRF8の役割2015
Author(s)
佐々木悠, 黒滝大翼, 大里直樹, 佐藤英明, 佐々木泉, 小泉真一, Hongsheng Wang, 金田智香, 西山 晃, 改正恒康, 油谷浩幸, Herbert C. Morse III, Keiko Ozato, 田村智彦
Organizer
第11回麒麟塾
Place of Presentation
コクヨホール（東京都港区）
Year and Date
2015-07-11
Related Report
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[Presentation] 転写因子IRF8による好塩基球分化制御機構の解明2015
Author(s)
黒滝大翼, 佐々木悠, 大里直樹, 佐藤英明, 佐々木泉, 小泉真一, Hongsheng Wang, 金田智香, 西山 晃, 改正恒康, 油谷浩幸, Herbert C. Morse III, Keiko Ozato, 田村智彦
Organizer
第26回生体防御学会学術総会
Place of Presentation
生涯学習センター（東京都台東区）
Year and Date
2015-07-10
Related Report
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