Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex
Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex
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DOI：
10.1038/ncb1637
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发表时间：
2007-10-01
影响因子：
21.3
通讯作者：
Orlando, Valerio
中科院分区：
文献类型：
--
作者：
Lanzuolo, Chiara;Roure, Virginie;Orlando, Valerio
在果蝇中，Polycomb组基因（PcGs）及其靶序列（Polycomb反应元件（PRE））的功能是传递转录程序的有丝分裂遗传性，特别是基因沉默。作为相关机制的一部分，PRE被认为通过在细胞核中建立更高级的结构来介导这种转录记忆功能。为了解决这个问题，我们分析了在体内的三维结构的同源异型基因座双胸复合体（BX-C）结合染色体构象捕获（3C）与荧光原位杂交（FISH）和FISH免疫染色（FISH-I）分析。我们发现，在抑制状态下，所有已被证明与PcG蛋白结合的主要元素，包括PRE和核心启动子，都在一定距离内相互作用，从而产生拓扑复杂的结构。我们表明，这种结构是重要的表观遗传沉默的BX-C，因为我们发现，在高阶结构的主要变化必须发生稳定地保持替代转录状态，而组蛋白修饰和PcG蛋白的水平降低确定表观遗传开关，只有部分遗传。
In Drosophila, the function of the Polycomb group genes ( PcGs) and their target sequences ( Polycomb response elements ( PREs)) is to convey mitotic heritability of transcription programmes-in particular, gene silencing. As part of the mechanisms involved, PREs are thought to mediate this transcriptional memory function by building up higher-order structures in the nucleus. To address this question, we analysed in vivo the three-dimensional structure of the homeotic locus bithorax complex ( BX-C) by combining chromosome conformation capture (3C) with fluorescent in situ hybridization ( FISH) and FISH immunostaining ( FISH-I) analysis. We found that, in the repressed state, all major elements that have been shown to bind PcG proteins, including PREs and core promoters, interact at a distance, giving rise to a topologically complex structure. We show that this structure is important for epigenetic silencing of the BX-C, as we find that major changes in higher-order structures must occur to stably maintain alternative transcription states, whereas histone modification and reduced levels of PcG proteins determine an epigenetic switch that is only partially heritable.