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首页> 外文期刊>Molecular and Cellular Biology >Antagonistic Regulation of β-Globin Gene Expression by Helix-Loop-Helix Proteins USF and TFII-I
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Antagonistic Regulation of β-Globin Gene Expression by Helix-Loop-Helix Proteins USF and TFII-I

机译:螺旋环蛋白USF和TFII-1对β球蛋白基因表达的拮抗作用

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The human β-globin genes are expressed in a developmental stage-specific manner in erythroid cells. Gene-proximal cis-regulatory DNA elements and interacting proteins restrict the expression of the genes to the embryonic, fetal, or adult stage of erythropoiesis. In addition, the relative order of the genes with respect to the locus control region contributes to the temporal regulation of the genes. We have previously shown that transcription factors TFII-I and USF interact with the β-globin promoter in erythroid cells. Herein we demonstrate that reducing the activity of USF decreased β-globin gene expression, while diminishing TFII-I activity increased β-globin gene expression in erythroid cell lines. Furthermore, a reduction of USF activity resulted in a significant decrease in acetylated H3, RNA polymerase II, and cofactor recruitment to the locus control region and to the adult β-globin gene. The data suggest that TFII-I and USF regulate chromatin structure accessibility and recruitment of transcription complexes in the β-globin gene locus and play important roles in restricting β-globin gene expression to the adult stage of erythropoiesis.
机译:人β-珠蛋白基因在红系细胞中以发育阶段特异性的方式表达。基因近端 cis 调控性DNA元件和相互作用的蛋白质将基因的表达限制在红细胞生成的胚胎,胎儿或成年阶段。另外,基因相对于基因座控制区的相对顺序有助于基因的时间调控。先前我们已经表明,转录因子TFII-1和USF与类红细胞中的β-珠蛋白启动子相互作用。在本文中,我们证明了降低USF的活性会降低类红细胞细胞系中β-珠蛋白基因表达,而减少TFII-I活性则会增加β-珠蛋白基因表达。此外,USF活性的降低导致乙酰化的H3,RNA聚合酶II和辅因子募集到基因座控制区和成年β-珠蛋白基因的显着减少。数据表明,TFII-I和USF调节染色质结构的可及性和β-珠蛋白基因位点转录复合物的募集,并且在将β-珠蛋白基因表达限制在红细胞生成的成年阶段中起重要作用。

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