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首页> 外文期刊>Molecular and Cellular Biology >Ikaros and GATA-1 Combinatorial Effect Is Required for Silencing of Human γ-Globin Genes
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Ikaros and GATA-1 Combinatorial Effect Is Required for Silencing of Human γ-Globin Genes

机译：Ikaros和GATA-1组合效应是人类γ-球蛋白基因沉默所必需的

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During development and erythropoiesis, globin gene expression is finely modulated through an important network of transcription factors and chromatin modifying activities. In this report we provide in vivo evidence that endogenous Ikaros is recruited to the human β-globin locus and targets the histone deacetylase HDAC1 and the chromatin remodeling protein Mi-2 to the human γ-gene promoters, thereby contributing to γ-globin gene silencing at the time of the γ- to β-globin gene transcriptional switch. We show for the first time that Ikaros interacts with GATA-1 and enhances the binding of the latter to different regulatory regions across the locus. Consistent with these results, we show that the combinatorial effect of Ikaros and GATA-1 impairs close proximity between the locus control region and the human γ-globin genes. Since the absence of Ikaros also affects GATA-1 recruitment to GATA-2 promoter, we propose that the combinatorial effect of Ikaros and GATA-1 is not restricted to globin gene regulation.
机译：在发育和促红细胞生成过程中，通过重要的转录因子和染色质修饰活性网络，可调节珠蛋白基因的表达。在本报告中，我们提供了体内证据，证明内源性Ikaros被募集到人β珠蛋白基因座，并将组蛋白脱乙酰基酶HDAC1和染色质重塑蛋白Mi-2靶向人γ基因启动子，从而导致γ珠蛋白基因沉默在从γ-到β-珠蛋白基因的转录转换时。我们首次展示了Ikaros与GATA-1相互作用并增强了GATA-1与整个基因座不同调控区域的结合。与这些结果一致，我们表明Ikaros和GATA-1的组合效应削弱了基因座控制区和人类γ珠蛋白基因之间的紧密接近。由于缺少Ikaros还影响GATA-1向GATA-2启动子的募集，因此我们建议Ikaros和GATA-1的组合作用不限于球蛋白基因调控。

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