Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factors
Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factors
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DOI：
10.1093/emboj/cdf527
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发表时间：
2002-10-01
期刊：
影响因子：
11.4
通讯作者：
Blobel, GA
中科院分区：
文献类型：
--
作者：
Wang, X;Crispino, JD;Blobel, GA
转录因子加塔-1及其辅因子FOG-1对红系细胞和巨核细胞的正常发育是必需的。FOG-1可刺激或抑制加塔-1活性，这取决于细胞和启动子环境。加塔-1-FOG-1复合物如何控制巨核细胞和红系细胞中不同基因组的表达尚不清楚。在这里，我们研究的巨核细胞限制性激活的α IIb基因的分子基础。FOG-1以需要它们直接物理相互作用的方式刺激加塔-1依赖性α IIb基因表达。加塔-1-FOG-1复合物的转录输出由与相邻Ets元件结合的造血Ets蛋白Fli-1决定。染色质免疫沉淀实验表明，加塔-1、FOG-1和Fli-1在体内共占据α IIb启动子。在其启动子中携带串联加塔和Ets元件的几个额外的巨核细胞特异性基因的表达也取决于加塔-1和FOG-1之间的物理相互作用。我们的研究确定了加塔-1和FOG-1转录激活的分子背景，并可能解释串联加塔和Ets元件在许多巨核细胞表达基因的启动子中的发生。
The transcription factor GATA-1 and its cofactor FOG-1 are essential for the normal development of erythroid cells and megakaryocytes. FOG-1 can stimulate or inhibit GATA-1 activity depending on cell and promoter context. How the GATA-1-FOG-1 complex controls the expression of distinct sets of gene in megakaryocytes and erythroid cells is not understood. Here, we examine the molecular basis for the megakaryocyte-restricted activation of the alphaIIb gene. FOG-1 stimulates GATA-1-dependent alphaIIb gene expression in a manner that requires their direct physical interaction. Transcriptional output by the GATA-1-FOG-1 complex is determined by the hematopoietic Ets protein Fli-1 that binds to an adjacent Ets element. Chromatin immunoprecipitation experiments show that GATA-1, FOG-1 and Fli-1 cooccupy the alphaIIb promoter in vivo. Expression of several additional megakaryocyte-specific genes that bear tandem GATA and Ets elements in their promoters also depends on the physical interaction between GATA-1 and FOG-1. Our studies define a molecular context for transcriptional activation by GATA-1 and FOG-1, and may explain the occurrence of tandem GATA and Ets elements in the promoters of numerous megakaryocyte-expressed genes.