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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A major role for the TATA box in recruitment of chromatin modifying complexes to a globin gene promoter
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A major role for the TATA box in recruitment of chromatin modifying complexes to a globin gene promoter

机译:TATA盒在将染色质修饰复合物募集到球蛋白基因启动子中的主要作用

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摘要

The developmentally regulated mammalian beta-globin genes are activated by a distant locus control region/enhancer. To understand the role of chromatin remodeling complexes in this activation, we used stably replicated chromatin templates, in which transcription activation of the human embryonic epsilon-globin gene depends on the tandem Maf-recognition elements (MAREs) within the beta-globin locus control region HS2 enhancer, to which the erythroid factor NF-E2 binds. The HS2 MAREs are required for nucleosome mobilization and histone hyperacetylation at the distant promoter. Nucleosome mobilization also requires the promoter TATA box, and is independent of histone hyperacetylation. In contrast, promoter hyperacetylation requires the promoter GATA-1, and CACC-factor activator motifs, as well as the TATA box. ChlP analysis reveals that NF-E2 is associated with the active epsilon-globin promoter, which lacks an NF-E2 binding sequence, in a TATA box and HS2/MARE-dependent fashion. NF-E2 association with the epsilon-globin promoter coincides with that of RNA polymerase II at both regulatory sites. The results emphasize MARE-TATA box interactions in the recruitment of complexes modifying promoter chromatin for transcription activation and imply close physical interaction between widely separated regulatory sequences mediated through these sites. [References: 63]
机译:发育受调节的哺乳动物β-珠蛋白基因被远处的基因座控制区/增强子激活。为了了解染色质重塑复合物在这种激活中的作用,我们使用了稳定复制的染色质模板,其中人类胚胎ε-珠蛋白基因的转录激活取决于β-珠蛋白基因座控制区内的串联Maf-识别元件(MARE)。红系因子NF-E2结合的HS2增强剂。 HS2 MARE是远距离启动子上核小体动员和组蛋白超乙酰化所必需的。核小体动员也需要启动子TATA框,并且独立于组蛋白超乙酰化。相反,启动子过度乙酰化需要启动子GATA-1和CACC因子激活子基序,以及TATA框。 ChlP分析显示,NF-E2以TATA盒和HS2 / MARE依赖性的方式与活性ε-珠蛋白启动子相关,该启动子缺乏NF-E2结合序列。与ε-珠蛋白启动子的NF-E2缔合与两个调控位点的RNA聚合酶II的缔合一致。结果强调在募集修饰启动子染色质以激活转录的复合物中募集MARE-TATA盒相互作用,并暗示通过这些位点介导的广泛分离的调控序列之间存在紧密的物理相互作用。 [参考:63]

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