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Abstract：
It is currently assumed that 3D chromosomal organization plays a central role in transcriptional control. However, depletion of cohesin and CTCF affects the steady-state levels of only a minority of transcripts. Here, we use high-resolution Capture Hi-C to interrogate the dynamics of chromosomal contacts of all annotated human gene promoters upon degradation of cohesin and CTCF. We show that a majority of promoter-anchored contacts are lost in these conditions, but many contacts with distinct properties are maintained, and some new ones are gained. The rewiring of contacts between promoters and active enhancers upon cohesin degradation associates with rapid changes in target gene transcription as detected by SLAM sequencing (SLAM-seq). These results provide a mechanistic explanation for the limited, but consistent, effects of cohesin and CTCF depletion on steady-state transcription and suggest the existence of both cohesin-dependent and -independent mechanisms of enhancer-promoter pairing.
摘要：
目前认为3D染色体组织在转录控制中起着核心作用。然而,粘附素和CTCF的消耗仅影响少数转录本的稳态水平。这里,我们使用高分辨率CaptureHi-C来询问在粘附素和CTCF降解时所有注释的人类基因启动子的染色体接触动力学。我们表明，大多数启动子锚定的接触在这些条件下丢失，但是保持了许多具有不同属性的联系，并获得了一些新的。粘附素降解时启动子和活性增强子之间的接触重新布线与通过SLAM测序（SLAM-seq）检测到的靶基因转录的快速变化有关。这些结果为有限的，但始终如一，粘附蛋白和CTCF耗竭对稳态转录的影响，表明存在增强子-启动子配对的粘附蛋白依赖性和非依赖性机制。
