Transcription-driven genome organization: a model for chromosome structure and the regulation of gene expression tested through simulations.
Transcription-driven genome organization: a model for chromosome structure and the regulation of gene expression tested through simulations.
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DOI：
10.1093/nar/gky763
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发表时间：
2018-11-02
影响因子：
14.9
通讯作者：
Marenduzzo D
中科院分区：
文献类型：
--
作者：
Cook PR;Marenduzzo D
当前的人类基因组折叠模型看到了一个层次结构，从染色体区域向下延伸，通过 A/B 区室和拓扑关联域 (TAD)，到达由粘连蛋白和 CTCF 稳定的接触域。然而，这种折叠背后的分子机制以及折叠影响转录活性的方式仍然不清楚。在这里，我们回顾了驱动与长聚合物结合的蛋白质形成被环包围的簇的物理原理，并为组织决定功能的方式提出了一个简洁而全面的模型。我们认为活性 RNA 聚合酶簇及其转录因子是主要的结构特征；然后，接触域、TAD 和区室仅反映一个或多个环和簇。我们建议将基因束缚在包含适当因子的簇（转录工厂）附近，以增加发射频率，并为当前有关增强子、超级增强子、边界和 eQTL（表达数量性状位点）作用的许多难题提供解决方案。因此，任何基因的活性都直接受到 3D 空间中其周围其他转录单元活性的影响，这得到了与长聚合物上同源位点结合的转录因子的布朗动力学模拟的支持。
Current models for the folding of the human genome see a hierarchy stretching down from chromosome territories, through A/B compartments and topologically-associating domains (TADs), 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.
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影响因子：
64.5
作者：
Dekker J;Mirny L
通讯作者：
Mirny L
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
4.6
作者：
Cho WK;Jayanth N;Mullen S;Tan TH;Jung YJ;Cissé II
通讯作者：
Cissé II
影响因子：
17.1
作者：
Chen, Xuanze;Wei, Mian;Sun, Yujie
通讯作者：
Sun, Yujie
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK