Long-range enhancer-promoter interactions in the Scr-Antp interval of the Drosophila Antennapedia complex
Long-range enhancer-promoter interactions in the Scr-Antp interval of the Drosophila Antennapedia complex
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DOI：
10.1073/pnas.1233791100
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发表时间：
2003-08-19
影响因子：
11.1
通讯作者：
Levine, M
中科院分区：
文献类型：
--
作者：
Calhoun, VC;Levine, M
长程增强子-启动子相互作用常见于复杂的基因位点，例如 Hox 基因和球蛋白基因。在果蝇触角复合体中，T1 增强子绕过邻近的 ftz 基因并与远处的 Scr 启动子相互作用，激活后头节的表达。先前的研究鉴定了一个 450 bp 的启动子近端序列，即束缚元件，它对于 T1-Scr 相互作用至关重要。为了更全面地了解各个增强子如何选择性地与适当的靶基因相互作用，我们使用生物信息学方法来识别大约 50 kb Scr-Antp 间隔内的新顺式调节 DNA。鉴定出三个先前未表征的调控元件：距离近端束缚序列 >40 kb 的远端 T1 束缚序列、排除不适当增强子激活 Scr 的阻遏元件，以及指导条带 1 和 5 范围内表达的新 ftz 增强子。Scr-Antp 间隔中的许多调控 DNA 都被转录，包括近端 DNA。 和远端栓系元件。我们认为，束缚元件之间的同型相互作用可以稳定发育过程中的长程 T1-Scr 相互作用。
Long-range enhancer-promoter interactions are commonly seen in complex genetic loci such as Hox genes and globin genes. In the case of the Drosophila Antennapedia complex, the T1 enhancer bypasses the neighboring ftz gene and interacts with the distant Scr promoter to activate expression in posterior head segments. Previous studies identified a 450-bp promoter-proximal sequence, the tethering element, which is essential for T1-Scr interactions. To obtain a more comprehensive view of how individual enhancers selectively interact with appropriate target genes, we used bioinformatic methods to identify new cis-regulatory DNAs in the approximate to50-kb Scr-Antp interval. Three previously uncharacterized regulatory elements were identified: a distal T1 tethering sequence mapping >40 kb from the proximal tethering sequence, a repressor element that excludes activation of Scr by inappropriate enhancers, and anew ftz enhancer that directs expression within the limits of stripes 1 and 5. Many of the regulatory DNAs in the Scr-Antp interval are transcribed, including the proximal and distal tethering elements. We suggest that homotypic interactions between the tethering elements stabilize long-range T1-Scr interactions during development.