CTCF organizes inter-A compartment interactions through RYBP-dependent phase separation
CTCF organizes inter-A compartment interactions through RYBP-dependent phase separation
复制标题
CTCF 通过 RYBP 依赖性相分离组织 A 区室间相互作用
DOI：
10.1038/s41422-022-00676-0
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发表时间：
2022-06-29
期刊：
影响因子：
44.1
通讯作者：
Ding，Junjun
中科院分区：
文献类型：
--
作者：
Wei，Chao;Jia，Lumeng;Ding，Junjun
染色质在空间上被组织成不同水平的三维结构，包括A/B区室、拓扑关联结构域和环。经典的CTCF介导的环挤出模型可以解释环的形成。然而，远距离染色质相互作用（如A-A区室之间的相互作用）的组织机制仍然知之甚少。在这里，我们表明，不同于典型的环挤出模型，RYBP介导的相分离的CTCF组织间的A室相互作用。基于此模型，我们设计并验证了一种诱导性CTCF相分离系统，该系统可促进A区室间的相互作用，提高胚胎干细胞的自我更新能力，并抑制其向神经前体细胞的分化。这些发现支持了CTCF在通过相分离组织长距离染色质相互作用中的新的和非经典的作用。
Chromatin is spatially organized into three-dimensional structures at different levels including A/B compartments, topologically associating domains and loops. The canonical CTCF-mediated loop extrusion model can explain the formation of loops. However, the organization mechanisms underlying long-range chromatin interactions such as interactions between A–A compartments are still poorly understood. Here we show that different from the canonical loop extrusion model, RYBP-mediated phase separation of CTCF organizes inter-A compartment interactions. Based on this model, we designed and verified an induced CTCF phase separation system in embryonic stem cells (ESCs), which facilitated inter-A compartment interactions, improved self-renewal of ESCs and inhibited their differentiation toward neural progenitor cells. These findings support a novel and non-canonical role of CTCF in organizing long-range chromatin interactions via phase separation.