Jones G, Chu Y X, Schelling D, Jones D
Cellular and Molecular Biology Section, School of Biological Sciences, University of Kentucky, Lexington, KY 40506, USA.
Biochem J. 2000 Feb 15;346 Pt 1(Pt 1):233-40.
Transcription from the core promoter of the juvenile hormone esterase gene (-61 to +28) requires the presence of both an AT-rich motif (TATA box) and an initiator motif for any transcription to occur, when assayed by either transcription in vitro with lepidopteran Sf9 nuclear extracts or by transient-transfection assay in Sf9 cells. Additional gel-shift experiments indicated that at least one additional binding site is essential for transcription to occur. Mutational analysis in the transcription-in vitro and cell-transfection assays demonstrated that a 14-bp region from +13 to +27 relative to the transcription start site is also essential for transcription to occur. Whereas the wild-type core promoter is highly transcriptionally active, inclusion of additional flanking sequences to position -212 reduces that activity approx. 100-fold, and inclusion of the 5' region out to position -500 reduces transcription by 200-fold. The pattern of dependence on both the AT-rich motif and the initiator for detectable transcription, and the high innate activity being repressed by 5'-binding factors, was recapitulated in mosquito C7-10 cells. This study demonstrates that the cellular juvenile hormone esterase gene is organized as a composite core promoter, dependent on both TATA-box and initiator-binding factors, an organization that has been more commonly reported for viral promoters. This highly active composite core promoter is made more complex by the absolute dependence on the presence of a third site shortly downstream from the initiator, which is distinct from the 'downstream promoter element' described from some TATA-less genes. The juvenile hormone esterase gene thus appears to be a model of a cellular composite core promoter with a multipartite, indispensible requirement for not just both the TATA box and initiator, but also for at least a third core element as well.
当通过用鳞翅目Sf9细胞核提取物进行体外转录或通过在Sf9细胞中进行瞬时转染试验来检测时,保幼激素酯酶基因核心启动子(-61至+28)的转录需要富含AT的基序(TATA盒)和起始子基序同时存在,才能发生任何转录。额外的凝胶迁移实验表明,至少一个额外的结合位点对于转录的发生是必不可少的。体外转录和细胞转染试验中的突变分析表明,相对于转录起始位点从+13至+27的一个14bp区域对于转录的发生也是必不可少的。野生型核心启动子具有高度转录活性,而包含至-212位置的额外侧翼序列会使该活性降低约100倍,而包含至-500位置的5'区域会使转录降低200倍。在蚊子C7-10细胞中也重现了对富含AT的基序和起始子进行可检测转录的依赖性模式,以及5'结合因子抑制高内在活性的情况。这项研究表明,细胞保幼激素酯酶基因被组织成一个复合核心启动子,依赖于TATA盒和起始子结合因子,这种组织方式在病毒启动子中更为常见。这种高度活跃的复合核心启动子因绝对依赖于起始子下游紧邻的第三个位点的存在而变得更加复杂,该位点不同于一些无TATA基因中描述的“下游启动子元件”。因此,保幼激素酯酶基因似乎是一个细胞复合核心启动子的模型,它不仅对TATA盒和起始子,而且对至少第三个核心元件都有多重、不可或缺的需求。