Chromatin insulator and the promoter targeting sequence modulate the timing of long-range enhancer-promoter interactions in the Drosophila embryo.
Chromatin insulator and the promoter targeting sequence modulate the timing of long-range enhancer-promoter interactions in the Drosophila embryo.
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染色质绝缘子和启动子靶向序列调节果蝇胚胎中长程增强子-启动子相互作用的时间。
DOI：
10.1016/j.ydbio.2009.12.029
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发表时间：
2010-03-15
影响因子：
2.7
通讯作者：
Zhou, Jumin
中科院分区：
文献类型：
--
作者：
Lin, Qing;Lin, Lan;Zhou, Jumin
同源异型基因对果蝇胚胎发育过程中前后轴沿着的形成是必不可少的。这些基因的表达时间和水平对于正确规范片段身份至关重要。Abdominal-B（Abd-B）基因首先在最后的腹部节中以高水平检测到，然后逐渐以较低的水平出现在腹前节中。影响这种表达模式的调节突变在腹部产生同源异型转化。来自Abd-B位点的启动子靶向序列（PTS）克服了绝缘子的增强子阻断效应，并促进转基因果蝇中的长距离增强子-启动子相互作用§。在本研究中，我们发现，通过插入一个9.5kb的3'端Abd-B调控区，该调控区含有前突蛋白8（Fab-8）绝缘子和PTS元件，可以延迟IAB 5增强子对转基因的激活。我们发现，延迟是由PTS和绝缘体引起的，并且它不是特定于测试的增强子或启动子。基于这些发现，我们假设远程增强子的延迟是负责的Abd-B的表达模式，这是至少部分地由于PTS元件和染色质边界的调节活动。
The homeotic genes are essential to the patterning of the anterior-posterior axis along the developing Drosophila embryo. The expression timing and levels of these genes are crucial for the correct specification of segmental identity. The Abdominal-B (Abd-B) gene is first detected in the most posterior abdominal segments at high levels and gradually appears in progressively anterior abdominal segments in lower amounts. Regulatory mutations affecting this expression pattern produce homeotic transformations in the abdomen. The Promoter Targeting Sequences (PTS) from Abd-B locus overcome the enhancer blocking effect of insulators and facilitate long-range enhancer-promoter interactions in transgenic flies §. In this study, we found that transgene activation by the IAB5 enhancer can be delayed by inserting a 9.5kb 3’ Abd-B regulatory region containing the Frontabdominal-8 (Fab-8) insulator and the PTS element. We found that the delay is caused by the PTS and an insulator, and it is not specific to the enhancer or the promoter tested. Based on these findings, we hypothesize that the delay of remote enhancers is responsible for the Abd-B expression pattern, which is at least in part due to the regulatory activities of the PTS elements and chromatin boundaries.
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