How distal regulatory elements control gene transcription and chromatin topology is not clearly defined, yet these processes are closely linked in lineage specification during development. Through allele-specific genome editing and chromatin interaction analyses of the Sox2 locus in mouse embryonic stem cells, we found a striking disconnection between transcriptional control and chromatin architecture. We traced nearly all Sox2 transcriptional activation to a small number of key transcription factor binding sites, whose deletions have no effect on promoter–enhancer interaction frequencies or topological domain organization. Local chromatin architecture maintenance, including at the topologically associating domain (TAD) boundary downstream from the Sox2 enhancer, is widely distributed over multiple transcription factor-bound regions and maintained in a CTCF-independent manner. Furthermore, partial disruption of promoter–enhancer interactions by ectopic chromatin loop formation has no effect on Sox2 transcription. These findings indicate that many transcription factors are involved in modulating chromatin architecture independently of CTCF.

中文翻译：

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转录调控和染色质结构维护是 Sox2 基因座的解耦功能


远端调控元件如何控制基因转录和染色质拓扑结构尚不清楚，但这些过程在发育过程中的谱系规范中密切相关。通过对小鼠胚胎干细胞中Sox2位点的等位基因特异性基因组编辑和染色质相互作用分析，我们发现转录控制和染色质结构之间存在显着的脱节。我们将几乎所有Sox2转录激活追溯到少数关键转录因子结合位点，这些位点的删除对启动子-增强子相互作用频率或拓扑结构域组织没有影响。局部染色质结构的维持，包括Sox2增强子下游的拓扑关联域 (TAD) 边界，广泛分布在多个转录因子结合区域，并以不依赖 CTCF 的方式维持。此外，异位染色质环形成对启动子-增强子相互作用的部分破坏对Sox2转录没有影响。这些发现表明许多转录因子独立于 CTCF 参与调节染色质结构。