Spicuglia Salvatore, Kumar Sanjeev, Yeh Jung-Hua, Vachez Elodie, Chasson Lionel, Gorbatch Sophie, Cautres Julie, Ferrier Pierre
Centre d'Immunologie de Marseille-Luminy, INSERM CNRS, Université de la Méditerranée, Case 906, 13288 Cedex 09, Marseille, France.
Mol Cell. 2002 Dec;10(6):1479-87. doi: 10.1016/s1097-2765(02)00791-8.
Activation of the pDbeta1 promoter at the TCRbeta locus requires a functional distal enhancer, Ebeta. Here, we have analyzed the mechanism of promoter activation in thymocytes from mice containing or lacking Ebeta. We found that pDbeta1 shows a complex profile of transcription factor and chromatin remodeling complex occupancy even at Ebeta(-) alleles. The presence of Ebeta, however, results in a few specific changes in factor occupancy at the promoter. These differences correlate with localized alterations in histone modifications and in the recruitment of the basal transcriptional machinery. In addition, Ebeta is also bound by CBP and Pol II, suggesting a mechanism for delivery of a holoenzyme complex to the pDbeta1 promoter. These results illustrate a specialized, long-range function of an enhancer in the hierarchical events that regulate assembly of a cell type-specific promoter.
TCRβ基因座处pDbeta1启动子的激活需要一个功能性的远端增强子Ebeta。在此,我们分析了含有或缺乏Ebeta的小鼠胸腺细胞中启动子激活的机制。我们发现,即使在Ebeta(-)等位基因处,pDbeta1也显示出转录因子和染色质重塑复合物占据的复杂图谱。然而,Ebeta的存在会导致启动子处因子占据的一些特定变化。这些差异与组蛋白修饰的局部改变以及基础转录机制的募集相关。此外,Ebeta还与CBP和Pol II结合,提示了一种将全酶复合物递送至pDbeta1启动子的机制。这些结果说明了增强子在调节细胞类型特异性启动子组装的分级事件中的一种特殊的远程功能。