聚合酶介导的环挤压的通用动力学

Thomas Sabate, Benoit Lelandais, Marie-Cecile Robert, Michael Szalay, Jean-Yves Tinevez, Edouard Bertrand, Christophe Zimmer
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引用次数: 0

摘要

大多数动物基因组都被划分为拓扑关联区(TAD),由凝聚素介导的环挤压形成,并由趋同取向的 CTCF 位点定义。在体内,环挤压及其调控的动态特征仍然不甚明了。在这里,我们追踪了活人细胞中的 TAD 锚点,以可视化和量化多个内源基因组区域中依赖于粘合素的环挤出。我们发现,TADs 是一种动态结构,其锚大约每小时靠近一次,持续时间为 6-19 分钟(约占 16%)。TADs 不断受到多个凝聚素复合物的挤压,以每秒约 0.1 kb 的速度挤出环。值得注意的是,尽管染色质区域之间的 Hi-C 模式差异很大,但它们的动态与相同的密度、停留时间和凝聚素速度是一致的。我们的研究结果表明,TAD 的动态主要受 CTCF 位点位置和亲和力的支配,这使得全基因组范围内依赖于凝聚素的相互作用的预测模型成为可能。
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Universal dynamics of cohesin-mediated loop extrusion
Most animal genomes are partitioned into Topologically Associating Domains (TADs), created by cohesin-mediated loop extrusion and defined by convergently oriented CTCF sites. The dynamics of loop extrusion and its regulation remains poorly characterized in vivo. Here, we tracked TAD anchors in living human cells to visualize and quantify cohesin-dependent loop extrusion across multiple endogenous genomic regions. We show that TADs are dynamic structures whose anchors are brought in proximity about once per hour and for 6-19 min (~16% of the time). TADs are continuously subjected to extrusion by multiple cohesin complexes, extruding loops at ~0.1 kb/s. Remarkably, despite strong differences of Hi-C patterns between the chromatin regions, their dynamics is consistent with the same density, residence time and speed of cohesin. Our results suggest that TAD dynamics is governed primarily by CTCF site location and affinity, which allows genome-wide predictive models of cohesin-dependent interactions.
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