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Suppressive effects of transcription factor GATA-1 on cell type-specific gene expression in dendritic cells

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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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Authors and Affiliations

  1. Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Naomi Shimokawa, Chiharu Nishiyama, Nobuhiro Nakano, Keiko Maeda, Ryuyo Suzuki, Mutsuko Hara, Tatsuo Fukai, Tomoko Tokura, Hideoki Ogawa & Ko Okumura

  2. Department of Pediatrics, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Ryuyo Suzuki

  3. Department of Dermatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Tatsuo Fukai

  4. Bio Medical Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Hiroaki Miyajima

  5. Department of Immunology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan

    Naomi Shimokawa & Atsuhito Nakao

Authors
  1. Naomi Shimokawa
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  2. Chiharu Nishiyama
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  3. Nobuhiro Nakano
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  4. Keiko Maeda
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  5. Ryuyo Suzuki
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  7. Tatsuo Fukai
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  8. Tomoko Tokura
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  9. Hiroaki Miyajima
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  10. Atsuhito Nakao
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  11. Hideoki Ogawa
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  12. Ko Okumura
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Correspondence to Chiharu Nishiyama.

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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

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