ABSTRACT Mammalian genome structure is closely linked to function. At the scale of kilobases to megabases, CTCF and cohesin organize the genome into chromatin loops. Mechanistically, cohesin is proposed to extrude chromatin loops bidirectionally until it encounters occupied CTCF DNA-binding sites. Curiously, loops form predominantly between CTCF binding sites in a convergent orientation. How CTCF interacts with and blocks cohesin extrusion in an orientation-specific manner has remained a mechanistic mystery. Here, we review recent papers that have shed light on these processes and suggest a multi-step interaction between CTCF and cohesin. This interaction may first involve a pausing step, where CTCF halts cohesin extrusion, followed by a stabilization step of the CTCF-cohesin complex, resulting in a chromatin loop. Finally, we discuss our own recent studies on an internal RNA-Binding Region (RBRi) in CTCF to elucidate its role in regulating CTCF clustering, target search mechanisms and chromatin loop formation and future challenges.

中文翻译：

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CTCF 作为黏连蛋白介导的环挤出的边界因素：多步骤机制的证据

摘要哺乳动物基因组结构与功能密切相关。在千碱基到兆碱基的范围内，CTCF 和 cohesin 将基因组组织成染色质环。从机制上讲，cohesin 被提议双向挤压染色质环，直到遇到占据的 CTCF DNA 结合位点。奇怪的是，环主要在 CTCF 结合位点之间以收敛方向形成。CTCF 如何以特定方向的方式与黏连蛋白挤出相互作用并阻止黏附素挤出仍然是一个机制上的谜。在这里，我们回顾了最近阐明这些过程的论文，并提出了 CTCF 和 cohesin 之间的多步骤相互作用。这种相互作用可能首先涉及一个暂停步骤，其中 CTCF 停止 cohesin 挤出，然后是 CTCF-cohesin 复合物的稳定步骤，导致染色质环。最后，