Fsh–Pc–Sce complex mediates active transcription of Cubitus interruptus (Ci)
Fsh–Pc–Sce complex mediates active transcription of Cubitus interruptus (Ci)
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DOI：
10.1093/jmcb/mjy008
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发表时间：
2018-10
影响因子：
5.5
通讯作者：
Xiangdong Lv;Hao Chen;Shuo Zhang;Zhao Zhang;Chenyu Pan;Yuanxin Xia;Jialin Fan;Wenqing Wu
中科院分区：
文献类型：
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作者：
Xiangdong Lv;Hao Chen;Shuo Zhang;Zhao Zhang;Chenyu Pan;Yuanxin Xia;Jialin Fan;Wenqing Wu
Hedgehog(HH)信号通路在胚胎发育和成体组织动态平衡中发挥着重要作用。这种生物学功能是由转录因子Cubitus interruptus(Ci)介导的。然而，对效应器Ci本身的转录调控研究很少。通过基于RNAi的遗传筛选，我们确定雌性不育(1)同源异型(FSH)是一种转录共激活因子，直接激活Ci转录。生化分析表明FSH、性梳外区(SCE)和聚梳区(Pc)之间存在物理相互作用。功能分析进一步表明，Ci的表达同时需要Pc和Sce，这可能不是由Pc或Sce突变细胞中Ci的抑制子Engrailed(En)的去抑制所介导的。最后，我们提供的证据表明，Pc/SCE促进了FSH在Ci位点的结合，FSH和Pc之间的物理相互作用是FSH介导的Ci转录所必需的。综上所述，我们不仅揭示了Ci受FSH-Pc-SCE复合体的转录调控，而且为FSH和PcG蛋白在转录调控中的协同作用提供了证据。
The Hedgehog (Hh) signaling pathway plays important roles in both embryonic development and adult tissue homeostasis. Such biological functions are mediated by the transcription factor Cubitus interruptus (Ci). Yet the transcriptional regulation of the effector Ci itself is poorly investigated. Through an RNAi-based genetic screen, we identified that female sterile (1) homeotic (Fsh), a transcription co-activator, directly activates Ci transcription. Biochemistry assays demonstrated physical interactions among Fsh, Sex combs extra (Sce), and Polycomb (Pc). Functional assays further showed that both Pc and Sce are required for Ci expression, which is not likely mediated by the derepression of Engrailed (En), a repressor of Ci, in Pc or Sce mutant cells. Finally, we provide evidence showing that Pc/Sce facilitates the binding of Fsh at Ci locus and that the physical interaction between Fsh and Pc is essential for Fsh-mediated Ci transcription. Taken together, we not only uncover that Ci is transcriptionally regulated by Fsh-Pc-Sce complex but also provide evidence for the coordination between Fsh and PcG proteins in transcriptional regulation.