Elongation inhibition by DRB sensitivity-inducing factor is regulated by the A20 promoter via a novel negative element and NF-κB
Elongation inhibition by DRB sensitivity-inducing factor is regulated by the A20 promoter via a novel negative element and NF-κB
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DOI：
10.1128/mcb.24.6.2444-2454.2004
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发表时间：
2004-03-01
影响因子：
5.3
通讯作者：
Dikstein, R
中科院分区：
文献类型：
--
作者：
Ainbinder, E;Amir-Zilberstein, L;Dikstein, R
A20是NF-kappaB的直接早期靶基因。在NF-kappaB刺激之前，A20启动子与聚合酶II机制结合以允许快速转录激活。在这里，我们发现A20的基础转录在延伸水平上以启动子特异性的方式受到抑制。体外免疫缺失和体外培养细胞的RNA干扰表明，基底伸长抑制是由DRB敏感性诱导因子（DSIF）赋予的。我们已经确定了一个叫做ELIE的负上游启动子元件，它控制着DSIF的活性。值得注意的是，在NF-kappaB刺激后，DSIF对A20启动子的抑制持续存在，但现在它是由NF-kappaB而不是ELIE调节的。DSIF对另一个nf - kappab应答基因ikappabα也有类似的调控作用。这些发现揭示了DSIF抑制伸长和启动子结合转录因子之间的密切和动态关系。讨论了顺式作用元件对DSIF活性差异调控的潜在意义。
A20 is an immediate-early NF-kappaB target gene. Prior to NF-kappaB stimulation, the A20 promoter is bound by the polymerase II machinery to allow rapid transcription activation. Here we show that the basal A20 transcription is repressed at the level of elongation in a promoter-specific fashion. Immunodepletion in vitro and RNA interference in cultured cells suggest that the basal elongation inhibition is conferred by DRB sensitivity-inducing factor (DSIF). We have identified a negative upstream promoter element called ELIE that controls DSIF activity. Remarkably, following NF-kappaB stimulation, inhibition of the A20 promoter by DSIF persists, but it is now regulated by NF-kappaB rather than ELIE. Similar regulation by DSIF is shown for another NF-kappaB-responsive gene, the IkappaBalpha gene. These findings reveal an intimate and dynamic relationship between DSIF inhibition of elongation and promoter-bound transcription factors. The potential significance of the differential regulation of DSIF activity by cis-acting elements is discussed.