The HTLV-1 Tax protein: revealing mechanisms of transcriptional activation through histone acetylation and nucleosome disassembly.-猫眼课题宝

HTLV-1 Tax 蛋白：通过组蛋白乙酰化和核小体分解揭示转录激活机制。

DOI：

10.1016/j.bbagrm.2009.09.002

发表时间：

2010

期刊：

Biochimica et biophysica acta

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

Nyborg,JenniferK;Egan,Dinaida;Sharma,Neelam

人类t细胞白血病病毒1型（HTLV-1）编码的Tax蛋白是该病毒高水平转录所必需的。Tax功能严格依赖于细胞转录因子CREB （pCREB）的磷酸化形式，它们一起结合位于病毒启动子内的新型cAMP反应元件。dna结合的Tax/pCREB复合体招募细胞共激活因子CBP/p300，这是病毒基因表达所必需的。共激活因子通过其组蛋白乙酰转移酶活性，促进染色质结构的变化，从而允许转录激活。体内的Tax表达将p300募集到HTLV-1启动子上，并与整合的原病毒核小体的消耗相关。我们最近开发了一种新的体外染色质实验系统，该系统概括了在体内观察到的HTLV-1启动子核小体的排出。这些实验确定了Tax/pCREB募集CBP/p300，以及伴随的组蛋白乙酰化在核小体分解过程中的重要作用。这些观察结果具有特别重要的意义，因为Tax介导完整核小体八聚体的分解，而不依赖于转录活性和ATP利用。相反，核小体的排出完全依赖于乙酰辅酶a和组蛋白伴侣Nap1。在这篇综述中，我们将讨论HTLV-1、Tax转激活以及我们最近的发现，这些发现揭示了Tax在促进伴随病毒转录激活的染色质转移中的关键作用。我们将描述乙酰化依赖启动子核小体解体的现象，以及一种新兴的观点，即无核小体启动子区域的形成可能代表了真核生物转录激活的一般先决条件。

The human T-cell leukemia virus, type-1 (HTLV-1)-encoded Tax protein is required for high-level transcription of the virus. Tax function is strictly dependent upon the phosphorylated form of the cellular transcription factor CREB (pCREB), and together they bind novel cAMP response elements located within the viral promoter. The DNA-bound Tax/pCREB complex recruits the cellular coactivators CBP/p300, which are essential for viral gene expression. The coactivators, via their histone acetyltransferase activity, function to promote changes in chromatin architecture that are permissive to transcriptional activation. Tax expression in vivo recruits p300 to the HTLV-1 promoter and correlates with depletion of nucleosomes from the integrated provirus. We recently developed a novel in vitro, chromatin-based experimental system that recapitulates the eviction of nucleosomes from the HTLV-1 promoter observed in vivo. These assays establish the essential function of Tax/pCREB recruitment of CBP/p300, and concomitant histone acetylation, in the nucleosome disassembly process. These observations are of particular significance, as Tax mediates disassembly of the full nucleosome octamer independent of transcriptional activity and ATP utilization. Instead, nucleosome eviction is absolutely dependent upon acetyl CoA and the histone chaperone Nap1. In this review, we will discuss HTLV-1, Tax transactivation, and our recent findings that uncover the critical role of Tax in promoting chromatin transitions that accompany activation of viral transcription. We will describe the phenomenon of acetylation-dependent promoter nucleosome disassembly and the emerging view that the formation of nucleosome-free promoter regions may represent a general prerequisite for transcriptional activation in eukaryotes.