HIV-1 Tat directly binds to NFκB enhancer sequence:: role in viral and cellular gene expression
HIV-1 Tat directly binds to NFκB enhancer sequence:: role in viral and cellular gene expression
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DOI：
10.1093/nar/gkh289
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发表时间：
2004-02-01
影响因子：
14.9
通讯作者：
Mitra, D
中科院分区：
文献类型：
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作者：
Dandekar, DH;Ganesh, KN;Mitra, D
HIV-1 Tat蛋白通过结合被称为反激活子反应区（TAR）的新生RNA茎环结构，对感染和未感染细胞的细胞基因表达进行重编程，除了其反激活HIV-1长末端重复（LTR）启动子的主要功能外。它还通过将组蛋白乙酰转移酶募集到染色质上，导致组蛋白乙酰化，诱导原病毒ltr介导的基因表达的染色质重塑。此外，一些研究已经显示了令人信服的证据，表明Tat可以在没有TAR的情况下反激活HIV-1基因表达，其分子机制仍有待阐明。在这里，我们展示了Tat与核因子κ B （NFkappaB）增强子的直接相互作用，NFkappaB增强子是体外和体内许多细胞基因的全局调控序列。这种相互作用不仅为解释HIV-1中tar不依赖的转激活提供了新的分子基础，而且还指出了Tat介导的细胞基因调节的潜在机制。
HIV-1 Tat protein reprograms cellular gene expression of infected as well as uninfected cells apart from its primary function of transactivating HIV-1 long terminal repeat (LTR) promoter by binding to a nascent RNA stem-loop structure known as the transactivator response region (TAR). Tat also induces chromatin remodeling of proviral LTR-mediated gene expression by recruiting histone acetyl transferases to the chromatin, which results in histone acetylation. Furthermore several studies have shown convincing evidence that Tat can transactivate HIV-1 gene expression in the absence of TAR, the molecular mechanism of which remains to be elucidated. Here we show a direct interaction of Tat with nuclear factor kappa B (NFkappaB) enhancer, a global regulatory sequence for many cellular genes both in vitro and in vivo. This interaction not only provides a novel molecular basis to explain TAR-independent transactivation in HIV-1, but also points toward the potential mechanism of Tat- mediated modulation of cellular genes.