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首页> 外文期刊>Molecular and Cellular Biology >The Histone Acetylase PCAF Is a Phorbol-Ester-Inducible Coactivator of the IRF Family That Confers Enhanced Interferon Responsiveness
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The Histone Acetylase PCAF Is a Phorbol-Ester-Inducible Coactivator of the IRF Family That Confers Enhanced Interferon Responsiveness

机译：组蛋白乙酰化酶PCAF是IRF家族的一种由酯类诱导的共激活因子，可增强干扰素的反应能力。

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Transcription factors of the interferon regulatory factor (IRF) family bind to the type I interferon (IFN)-responsive element (ISRE) and activate transcription from IFN-inducible genes. To identify cofactors that associate with IRF proteins, DNA affinity binding assays were performed with nuclear extracts prepared from tissue culture cells. The results demonstrated that the endogenous IRFs bound to the ISRE are complexed with the histone acetylases, PCAF, GCN5, and p300/CREB binding protein and that histone acetylase activities are accumulated on the IRF-ISRE complexes. By testing recombinant proteins, we show that PCAF directly binds to some but not all members of the IRF family through distinct domains of the two proteins. This interaction was functionally significant, since transfection of PCAF strongly enhanced IRF-1- and IRF-2-dependent promoter activities. Further studies showed that expression of PCAF and other histone acetylases was markedly induced in U937 cells upon phorbol ester treatment, which led to increased recruitment of PCAF to the IRF-ISRE complexes. Coinciding with the induction of histone acetylases, phorbol ester markedly enhanced IFN-α-stimulated gene expression in U937 cells. Supporting the role for PCAF in conferring IFN responsiveness, transfection of PCAF into U937 cells led to a large increase in IFN-α-inducible promoter activity. These results demonstrate that PCAF is a phorbol ester-inducible coactivator of the IRF proteins which contributes to the establishment of type I IFN responsiveness.
机译：干扰素调节因子（IRF）家族的转录因子与I型干扰素（IFN）响应元件（ISRE）结合并激活IFN诱导型基因的转录。为了鉴定与IRF蛋白相关的辅因子，对从组织培养细胞制备的核提取物进行了DNA亲和力结合测定。结果表明，与ISRE结合的内源性IRF与组蛋白乙酰化酶，PCAF，GCN5和p300 / CREB结合蛋白复合，并且组蛋白乙酰化酶活性在IRF-ISRE复合物中积累。通过测试重组蛋白，我们显示PCAF通过两种蛋白的不同结构域直接结合IRF家族的部分成员，但不是全部成员。这种相互作用在功能上很重要，因为转染PCAF可以大大增强IRF-1和IRF-2依赖的启动子活性。进一步的研究表明，佛波酯处理后，U937细胞中PCAF和其他组蛋白乙酰化酶的表达被明显诱导，这导致PCAF向IRF-ISRE复合物的募集增加。伴随着组蛋白乙酰化酶的诱导，佛波酯显着增强了U937细胞中IFN-α刺激的基因表达。为了支持PCAF在赋予IFN反应性中的作用，将PCAF转染到U937细胞中导致IFN-α诱导的启动子活性大大增加。这些结果证明，PCAF是IRF蛋白的佛波酯诱导的共激活剂，其有助于建立I型IFN应答性。

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