2014 Fiscal Year Final Research Report
Analysis of the role of transcription factors in monocyte development
| Project/Area Number |
24790322
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 単球分化 / 転写因子 / IRF8 |
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| Outline of Final Research Achievements |
We found that the IRF8-KLF4 transcription factor cascade is essential for monocyte development. During IRF8-dependent monocyte differentiation, the chromatin binding of IRF8 at promoter-distal regions induces the establishment of enhancers marked by histone H3 lysine 4 monomethylation (H3K4me1), thereby promoting the expression of monocyte-related genes including KLF4, which is essential for Ly6C+ monocyte development. In IRF8-deficient mice, monocyte development is as defective as that in KLF4-deficient mice. Moreover, mononuclear phagocyte progenitors in IRF8-deficient mice do not express KLF4. We also found that IRF8 suppresses the chromatin binding of C/EBPα, the transcription factor that promotes neutrophil differentiation, to restrain mononuclear phagocyte progenitors from differentiating into neutrophils.
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| Free Research Field |
免疫学
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