Stability and Dynamics of Polycomb Target Sites in Drosophila Development
Stability and Dynamics of Polycomb Target Sites in Drosophila Development
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DOI：
10.1371/journal.pgen.1000178
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发表时间：
2008-09-01
期刊：
影响因子：
4.5
通讯作者：
White, Robert
中科院分区：
文献类型：
--
作者：
Kwong, Camilla;Adryan, Boris;White, Robert
多梳组（PcG）和三胸组蛋白一起形成一个维护机制，负责稳定的遗传状态的基因活性。虽然最好的研究目标基因是Hox基因的双胸复合体，大量的关键发育基因也Polycomb（Pc）的目标，这表明了广泛的作用，这种维护机制在细胞命运的决定。我们已经研究了PcG蛋白的结合和基因表达的发育调控之间的联系，使用全基因组定位，以确定由PcG蛋白，Pc和Pleiohameotic（Pho），在果蝇胚胎和一个更受限制的组织，成虫盘的第三胸段的结合位点。我们的数据提供了支持的想法，Pho是一个一般组成部分的维护机器，因为大多数的Pc目标也与Pho绑定。我们发现，在一般情况下，相当大的发展稳定性的Pc和磷结合在靶基因，并观察到Pc/磷结合可以与表达和失活基因。特别是，在Hox复合物中，活性和非活性基因都具有显着的Pc和Pho结合。然而，与非活性基因相比，活性Hox基因显示减少和改变的结合谱。在发展过程中，Pc靶基因并不简单地不断与Pc/Pho结合，我们确定了一套基因胚胎和成虫盘之间具有明确的差异结合。使用现有的数据集，我们表明，特定的命运决定基因的血细胞谱系，活性状态的特点是缺乏Pc结合。总体而言，我们的分析表明，Pc/Pho结合和基因转录之间的动态关系。Pc/Pho结合不妨碍转录，但Pc/Pho结合水平在发育过程中发生变化，Pc/Pho结合的丧失可能与稳定的基因活性和失活有关。
Polycomb-group (PcG) and Trithorax-group proteins together form a maintenance machinery that is responsible for stable heritable states of gene activity. While the best-studied target genes are the Hox genes of the Antennapedia and Bithorax complexes, a large number of key developmental genes are also Polycomb ( Pc) targets, indicating a widespread role for this maintenance machinery in cell fate determination. We have studied the linkage between the binding of PcG proteins and the developmental regulation of gene expression using whole-genome mapping to identify sites bound by the PcG proteins, Pc and Pleiohomeotic (Pho), in the Drosophila embryo and in a more restricted tissue, the imaginal discs of the third thoracic segment. Our data provide support for the idea that Pho is a general component of the maintenance machinery, since the majority of Pc targets are also associated with Pho binding. We find, in general, considerable developmental stability of Pc and Pho binding at target genes and observe that Pc/Pho binding can be associated with both expressed and inactive genes. In particular, at the Hox complexes, both active and inactive genes have significant Pc and Pho binding. However, in comparison to inactive genes, the active Hox genes show reduced and altered binding profiles. During development, Pc target genes are not simply constantly associated with Pc/Pho binding, and we identify sets of genes with clear differential binding between embryo and imaginal disc. Using existing datasets, we show that for specific fate-determining genes of the haemocyte lineage, the active state is characterised by lack of Pc binding. Overall, our analysis suggests a dynamic relationship between Pc/Pho binding and gene transcription. Pc/Pho binding does not preclude transcription, but levels of Pc/Pho binding change during development, and loss of Pc/Pho binding can be associated with both stable gene activity and inactivity.