Abstract
To evaluate the effects of the transcription factor GATA-1 on determining cell fate between dendritic cell (DC) and mast cell (MC) lineages, GATA-1 was exogenously expressed in bone marrow-derived (BM) DCs. Exogenous expression of GATA-1 by a retrovirus in BMDCs inhibited expression of CD11c, CD80, CD86, and major histocompatibility complex class II with suppression of antigen-presenting ability and morphological changes toward granulocyte-like cells. Transcription of MC proteases and c-kit was markedly upregulated by GATA-1. Expression of IRF-4 and -8 was markedly suppressed, whereas PU.1 mRNA level was not affected by GATA-1. Chromatin immunoprecipitation assay showed that recruitment of PU.1 on the IRF-8 promoter was reduced in GATA-1-expressing DCs. These results indicate that GATA-1 suppresses PU.1 function but not PU.1 transcription. Thus, GATA-1 appears to determine cell fate by regulating several cell-specific transcription factors.
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Abbreviations
- BM:
-
Bone marrow-derived
- ChIP:
-
Chromatin immunoprecipitation
- DC:
-
Dendritic cells
- IRF:
-
Interferon regulatory factor
- MC:
-
Mast cells
- MCCPA:
-
Mast cell carboxypeptidase
- MCCP:
-
Mast cell protease
- MHC:
-
Major histocompatibility complex
- GFP:
-
Green fluorescence protein
- RT:
-
Reverse transcription
- PCR:
-
Polymerase chain reaction
- GM-CSF:
-
Granulocyte-macrophage colony-stimulatingfactor
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Acknowledgements
We would like to thank Dr. M. Yoshida for assistance with electron microscopy, Dr. T. Sakanishi for operating the cell-sorting system, and Dr. T. Kitamura for providing Plat-E. We also wish to thank the members of the Atopy Research Center and Department of Immunology, Juntendo University School of Medicine, for their helpful discussions. Finally, we are grateful to Drs. S. Kanada, W. Ng, Q.-H. Wang, D. P. Potaczek, and N. Kitamura, as well as Mr. H. Yokoyama, for their fruitful discussion and critical advice, and Ms. M. Matsumoto for her secretarial assistance. This work was supported in part by a Grant-in-Aid for Scientific Research (C) (to C. N.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
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Shimokawa, N., Nishiyama, C., Nakano, N. et al. Suppressive effects of transcription factor GATA-1 on cell type-specific gene expression in dendritic cells. Immunogenetics 62, 421–429 (2010). https://doi.org/10.1007/s00251-010-0444-1
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DOI: https://doi.org/10.1007/s00251-010-0444-1