Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains.
Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains.
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DOI：
10.1093/nar/gkw135
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发表时间：
2016-05-05
影响因子：
14.9
通讯作者：
Marenduzzo D
中科院分区：
文献类型：
--
作者：
Brackley CA;Johnson J;Kelly S;Cook PR;Marenduzzo D
生物物理学家正在模拟间期染色体的构象，通常是根据实验确定的接触频率来确定遗传图谱上遥远片段之间的相互作用强度。在这里，相反，我们开发了一个无拟合的最小模型：二价或多价的红色和绿色“转录因子”结合到珠串（“染色质”）中的同源位点，形成分子桥稳定环。在没有额外的明确的力量，分子动力学模拟表明，绑定因子自发集群红色与红色，绿色与绿色，但很少红色与绿色，让人想起转录工厂的结构。仅将两个转录因子（或蛋白质）与人类染色体的活性和非活性区域结合，就产生了与实验中所见非常相似的ROTRONIC、拓扑结构域和接触图。这种紧急的“桥接诱导的吸引力”被证明是一种强大的，简单的和通用的力量，能够在所有尺度上组织间期染色体。
Biophysicists are modeling conformations of interphase chromosomes, often basing the strengths of interactions between segments distant on the genetic map on contact frequencies determined experimentally. Here, instead, we develop a fitting-free, minimal model: bivalent or multivalent red and green ‘transcription factors’ bind to cognate sites in strings of beads (‘chromatin’) to form molecular bridges stabilizing loops. In the absence of additional explicit forces, molecular dynamic simulations reveal that bound factors spontaneously cluster—red with red, green with green, but rarely red with green—to give structures reminiscent of transcription factories. Binding of just two transcription factors (or proteins) to active and inactive regions of human chromosomes yields rosettes, topological domains and contact maps much like those seen experimentally. This emergent ‘bridging-induced attraction’ proves to be a robust, simple and generic force able to organize interphase chromosomes at all scales.