Depletion of architectural factors globally alters chromatin structure, but only modestly affects gene expression. We revisit the structure-function relationship using the inactive X chromosome (Xi) as a model. We investigate cohesin imbalances by forcing its depletion or retention using degron-tagged RAD21 (cohesin subunit) or WAPL (cohesin release factor). Interestingly, cohesin loss disrupts Xi superstructure, unveiling superloops between escapee genes, with minimal effect on gene repression. By contrast, forced cohesin retention markedly affects Xi superstructure and compromises spreading of Xist RNA-Polycomb complexes, attenuating Xi silencing. Effects are greatest at distal chromosomal ends, where looping contacts with the Xist locus are weakened. Surprisingly, cohesin loss created an "Xi superloop" and cohesin retention created "Xi megadomains" on the active X. Across the genome, a proper cohesin balance protects against aberrant inter-chromosomal interactions and tempers Polycomb-mediated repression. We conclude that a balance of cohesin eviction and retention regulates X-inactivation and inter-chromosomal interactions across the genome.

中文翻译：

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强制凝聚素驱逐和保留对X灭活和常染色体的影响

建筑因素的耗竭全局改变染色质结构，但仅适度影响基因表达。我们使用非活动X染色体（Xi）作为模型来重新探讨结构与功能的关系。我们通过使用地格隆标记的RAD21（粘着蛋白亚基）或WAPL（粘着蛋白释放因子）强迫其耗竭或保留来研究粘着蛋白失衡。有趣的是，粘着蛋白的丢失破坏了Xi的超结构，揭示了逃逸基因之间的超环，对基因抑制的影响最小。相比之下，强制黏附蛋白保留显着影响Xi的超结构并损害Xist RNA-Polycomb复合物的扩散，减弱Xi的沉默。在远端染色体末端的作用最大，与Xist基因座的环状接触减弱。出乎意料的是，粘着蛋白的损失产生了“ Xi超环” 在整个基因组中，适当的粘附素平衡可防止异常的染色体间相互作用，并抑制多梳介导的抑制。我们得出结论，凝聚素逐出和保留之间的平衡调节了基因组中的X失活和染色体间相互作用。