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

Naomi Shimokawa, Chiharu Nishiyama, Nobuhiro Nakano, Keiko Maeda, Ryuyo Suzuki, Mutsuko Hara, Tatsuo Fukai, Tomoko Tokura, Hiroaki Miyajima, Atsuhito Nakao, Hideoki Ogawa, Ko Okumura
Immunogenetics 2010, 62 (7): 421-9
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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