Suppressive effects of transcription factor GATA-1 on cell type-specific gene expression in dendritic cells
Suppressive effects of transcription factor GATA-1 on cell type-specific gene expression in dendritic cells
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DOI：
10.1007/s00251-010-0444-1
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发表时间：
2010-07-01
期刊：
影响因子：
3.2
通讯作者：
Okumura, Ko
中科院分区：
文献类型：
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作者：
Shimokawa, Naomi;Nishiyama, Chiharu;Okumura, Ko
为了评价转录因子加塔-1对决定树突状细胞（DC）和肥大细胞（MC）谱系之间的细胞命运的作用，将加塔-1外源性表达于骨髓来源的（BM）DC中。通过逆转录病毒在BMDCs中外源性表达加塔-1可抑制CD 11 c、CD 80、CD 86和主要组织相容性复合物II类的表达，并抑制抗原呈递能力和向粒细胞样细胞的形态学变化。MC蛋白酶和c-kit的转录被加塔-1显著上调。IRF-4和IRF-8的表达被显著抑制，而PU.1 mRNA水平不受加塔-1的影响。染色质免疫沉淀分析显示，在表达加塔-1的DC中，IRF-8启动子上的PU. 1的募集减少。这些结果表明，加塔-1抑制PU. 1功能，但不抑制PU. 1转录。因此，加塔-1似乎通过调节几种细胞特异性转录因子来决定细胞命运。
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.