Different modes of enhancer-specific regulation by Runt and Even-skipped during Drosophila segmentation.
Different modes of enhancer-specific regulation by Runt and Even-skipped during Drosophila segmentation.
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DOI：
10.1091/mbc.e16-09-0630
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发表时间：
2017-03-01
影响因子：
3.3
通讯作者：
Gergen JP
中科院分区：
文献类型：
--
作者：
Hang S;Gergen JP
果蝇slp1基因的表达依赖于两个顺式调控增强子之间的非加性相互作用。这些增强子通过阻止Pol II的募集或启动子-近端暂停Pol II的释放而受到抑制，这种抑制方式是增强子和转录因子特异性的，并且可以解释它们的非加性相互作用。果蝇草率配对1 （slp1）基因的初始异聚表达由两个不同的顺式调控DNA元件控制，它们以非加性的方式相互作用，整合由成对规则分割基因编码的转录因子的输入。我们对不同胚胎基因型中含有这些元件的报告基因进行了染色质免疫沉淀，以研究它们的调控机制。远端早期条纹元件（DESE）介导Runt的激活和抑制。我们发现，DESE对Runt的差异反应是由于扶湿tarazu （Ftz）抑制P-TEFb的募集和RNA聚合酶II （Pol II）暂停的调节作用。近端早期条纹元件（PESE）也受到Runt的抑制，但在这种情况下，Runt阻止PESE依赖的Pol II募集和预起始复合物（PIC）组装。PESE也受到even -skip （Eve）的抑制，但有趣的是，这种抑制涉及P-TEFb招募和启动子-近端Pol II暂停的调节。这些结果表明，Runt对slp1的抑制模式是增强子特异性的，而对slp1 PESE增强子的抑制模式是转录因子特异性的。我们提出了一个基于这些差异调控相互作用的模型，该模型解释了果蝇分割过程中PESE和DESE增强子之间的非加性相互作用。
Expression of the Drosophila slp1 gene depends on nonadditive interactions between two cis-regulatory enhancers. These enhancers are repressed by preventing either Pol II recruitment or release of promoter-proximal paused Pol II in a manner that is both enhancer and transcription factor specific and can account for their nonadditive interaction. The initial metameric expression of the Drosophila sloppy paired 1 (slp1) gene is controlled by two distinct cis-regulatory DNA elements that interact in a nonadditive manner to integrate inputs from transcription factors encoded by the pair-rule segmentation genes. We performed chromatin immunoprecipitation on reporter genes containing these elements in different embryonic genotypes to investigate the mechanism of their regulation. The distal early stripe element (DESE) mediates both activation and repression by Runt. We find that the differential response of DESE to Runt is due to an inhibitory effect of Fushi tarazu (Ftz) on P-TEFb recruitment and the regulation of RNA polymerase II (Pol II) pausing. The proximal early stripe element (PESE) is also repressed by Runt, but in this case, Runt prevents PESE-dependent Pol II recruitment and preinitiation complex (PIC) assembly. PESE is also repressed by Even-skipped (Eve), but, of interest, this repression involves regulation of P-TEFb recruitment and promoter-proximal Pol II pausing. These results demonstrate that the mode of slp1 repression by Runt is enhancer specific, whereas the mode of repression of the slp1 PESE enhancer is transcription factor specific. We propose a model based on these differential regulatory interactions that accounts for the nonadditive interactions between the PESE and DESE enhancers during Drosophila segmentation.