Transcription factor binding and histone modifications on the integrated proviral promoter in human T-cell leukemia virus-I-infected T-cells
Transcription factor binding and histone modifications on the integrated proviral promoter in human T-cell leukemia virus-I-infected T-cells
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DOI：
10.1074/jbc.m209566200
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发表时间：
2002-12-20
影响因子：
4.8
通讯作者：
Nyborg, JK
中科院分区：
文献类型：
--
作者：
Lemasson, I;Polakowski, NJ;Nyborg, JK
人类T细胞白血病病毒（HTLV-I）编码的Tax蛋白是一种有效的转录激活因子，可刺激整合前病毒的表达。生物化学研究表明，税收，与细胞转录因子，与病毒cAMP反应元件增强子元件相互作用，招募多效性共激活CREB结合蛋白和p300。这些共活化剂引起的组蛋白乙酰化在体外激活HTLV-1从染色质模板转录中起主要作用。然而，组蛋白修饰的程度和在体内结合在HTLV-1启动子的细胞调节蛋白的确切身份是未知的。染色质免疫沉淀分析用于研究在感染的T细胞（SLB-1）中整合的HTLV-1前病毒处的因子结合和组蛋白修饰。这些研究揭示了Tax、各种ATF/CREB和AP-1家族成员（CREB、CREB-2、ATF-1、ATF-2、c-Fos和c-Jun）以及p300和CREB结合蛋白在HTLV-1启动子处的存在。与这些共激活剂的结合一致，我们观察到组蛋白H3和H4乙酰化在前病毒基因组内的三个区域。组蛋白去乙酰化酶也存在于病毒启动子，并且在其抑制后，我们观察到HTLV-1启动子上组蛋白H4乙酰化的增加和伴随的病毒RNA的增加。总之，这些结果表明，各种转录激活因子，共激活因子，和组蛋白脱乙酰酶参与受感染的T细胞中的HTLV-I转录的调节。
The human T-cell leukemia virus (HTLV-I)-encoded Tax protein is a potent transcriptional activator that stimulates expression of the integrated provirus. Biochemical studies indicate that Tax, together with cellular transcription factors, interacts with viral cAMP-response element enhancer elements to recruit the pleiotropic coactivators CREB-binding protein and p300. Histone acetylation by these coactivators has been shown to play a major role in activating HTLV-I transcription from chromatin templates in vitro. However, the extent of histone modification and the precise identity of the cellular regulatory proteins bound at the HTLV-I promoter in vivo is not known. Chromatin immunoprecipitation analysis was used to investigate factor binding and histone modification at the integrated HTLV-I provirus in infected T-cells (SLB-1). These studies reveal the presence of Tax, a variety of ATF/CREB and AP-1 family members (CREB, CREB-2, ATF-1, ATF-2, c-Fos, and c-Jun), and both p300 and CREB-binding protein at the HTLV-I promoter. Consistent with the binding of these coactivators, we observed histone H3 and H4 acetylation at three regions within the proviral genome. Histone deacetylases were also present at the viral promoter and, following their inhibition, we observe an increase in histone H4 acetylation on the HTLV-I promoter and a concomitant increase in viral RNA. Together, these results suggest that a variety of transcriptional activators, coactivators, and histone deacetylases participate in the regulation of HTLV-I transcription in infected T-cells.