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

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,...

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Bibliographic Details
Published in:Immunogenetics (New York) 2010-07, Vol.62 (7), p.421-429
Main Authors: Shimokawa, Naomi, Nishiyama, Chiharu, Nakano, Nobuhiro, Maeda, Keiko, Suzuki, Ryuyo, Hara, Mutsuko, Fukai, Tatsuo, Tokura, Tomoko, Miyajima, Hiroaki, Nakao, Atsuhito, Ogawa, Hideoki, Okumura, Ko
Format: Article
Language:English
Subjects:
Allergology
Animals
B7-1 Antigen - metabolism
B7-2 Antigen - metabolism
Biomedical and Life Sciences
Biomedicine
Blotting, Western
Bone marrow
Bone Marrow Cells - metabolism
Cell Biology
Cell Differentiation
Cell Lineage
Cells, Cultured
Chromatin Immunoprecipitation
dendritic cells
Dendritic Cells - metabolism
Flow Cytometry
GATA-1
GATA1 Transcription Factor - genetics
Gene Expression Regulation - physiology
Gene Function
Human Genetics
Immunology
Interferon Regulatory Factors - genetics
Interferon Regulatory Factors - metabolism
IRF
mast cells
Mast Cells - metabolism
Mice
Mice, Inbred BALB C
Original Paper
Promoter Regions, Genetic - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
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Summary: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.
ISSN:0093-7711
1432-1211
DOI:10.1007/s00251-010-0444-1