A shared enhancer controls a temporal switch between promoters during Drosophila primary sex determination
A shared enhancer controls a temporal switch between promoters during Drosophila primary sex determination
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DOI：
10.1073/pnas.0805993105
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发表时间：
2008-11-25
影响因子：
11.1
通讯作者：
Erickson, James W.
中科院分区：
文献类型：
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作者：
Gonzalez, Alejandra N.;Lu, Hong;Erickson, James W.
Sex-lethal（Sxl）基因是果蝇体细胞性别决定的主要调控基因，通过自身调控Sxl前体mRNA的加工过程，使其稳定地保持在开启或关闭状态。正确的Sxl剪接模式的建立需要两个Sxl启动子的协调调节。这些启动子中的第一个，SxlPe，响应于两个X染色体的雌性剂量以产生Sxl蛋白的脉冲，其作用于来自第二个启动子SxlPm的前mRNA产物以建立剪接环。SxlPm是活跃的两性在整个大部分的发展，但没有什么是已知的SxlPm是如何表达的过渡期间，从X信号评估，以维持剪接。我们发现，SxlPm激活早在女性比男性在一系列的果蝇物种，它的表达与SxlPe在合胞胚盘阶段短暂重叠。SxlPm的激活依赖于将X染色体剂量传递给SxlPe的scute、daughterless和runt转录因子，但不依赖于X信号元件sisA和母体共阻遏物groucho。我们表明，DNA序列调节的响应SxlPe的X染色体剂量也控制性别差异的响应SxlPm。我们建议，Sxl蛋白及其前体mRNA底物的共表达促进了从转录到剪接控制的过渡，并且延迟了SxlPm在男性缓冲液中的激活，以对抗由X染色体信号强度波动引起的Sxl的不适当激活。
Sex-lethal (Sxl), the master regulatory gene of Drosophila somatic sex determination, is stably maintained in an on or an off state by autoregulatory control of Sxl premRNA processing. Establishment of the correct Sxl splicing pattern requires the coordinate regulation of two Sxl promoters. The first of these promoters, SxlPe, responds to the female dose of two X chromosomes to produce a pulse of Sxl protein that acts on the premRNA products from the second promoter, SxlPm, to establish the splicing loop. SxlPm is active in both sexes throughout most of development, but nothing is known about how SxlPm is expressed during the transition from X signal assessment to maintenance splicing. We found that SxlPm is activated earlier in females than in males in a range of Drosophila species, and that its expression overlaps briefly with that of SxlPe during the syncytial blastoderm stage. Activation of SxlPm depends on the scute, daughterless, and runt transcription factors, which communicate X chromosome dose to SxlPe, but is independent of the X signal element sisA and the maternal co-repressor groucho. We show that DNA sequences regulating the response of SxlPe to the X chromosome dose also control the sex-differential response of SxlPm. We propose that co-expression of Sxl protein and its premRNA substrate facilitates the transition from transcriptional to splicing control, and that delayed activation of SxlPm in males buffers against the inappropriate activation of Sxl by fluctuations in the strength of the X chromosome signal.