论文标题
转录驱动的基因组组织：染色体结构的模型和通过模拟测试的基因表达的调节
Transcription-driven genome organization: a model for chromosome structure and the regulation of gene expression tested through simulations
论文作者
论文摘要
当前的人基因组折叠模型看到，从染色体领土延伸到A/B室和TAD（拓扑结合的域），以通过粘粘膜和CTCF稳定下来。但是，这种折叠的基础机制以及折叠的方式影响转录活性，仍然晦涩难懂。在这里，我们回顾了将蛋白质绑定到长聚合物的物理原理，以围绕着循环包围，并为组织确定功能的方式提供了简约而全面的模型。我们认为，活性RNA聚合酶及其转录因子的簇是主要的建筑特征。然后，接触域，TAD和隔室只反映了一个或多个循环和簇。我们建议将一个接近包含适当因素的群集的基因（转录工厂）增加，以增加发射频率，并为许多当前难题提供有关增强剂，超级增强剂，边界和EQTL的作用的解决方案（表达式定量性状位点）。结果，任何基因的活性都受到3D空间中其他转录单元的活性的直接影响，这得到了布朗尼动力学模拟的转录因子的模拟，该动力学的转录因子与长聚合物上的同源位点结合。
Current models for the folding of the human genome see a hierarchy stretching down from chromosome territories, through A/B compartments and TADs (topologically-associating domains), to contact domains stabilized by cohesin and CTCF. However, molecular mechanisms underlying this folding, and the way folding affects transcriptional activity, remain obscure. Here we review physical principles driving proteins bound to long polymers into clusters surrounded by loops, and present a parsimonious yet comprehensive model for the way the organization determines function. We argue that clusters of active RNA polymerases and their transcription factors are major architectural features; then, contact domains, TADs, and compartments just reflect one or more loops and clusters. We suggest tethering a gene close to a cluster containing appropriate factors -- a transcription factory -- increases the firing frequency, and offer solutions to many current puzzles concerning the actions of enhancers, super-enhancers, boundaries, and eQTLs (expression quantitative trait loci). As a result, the activity of any gene is directly influenced by the activity of other transcription units around it in 3D space, and this is supported by Brownian-dynamics simulations of transcription factors binding to cognate sites on long polymers.
