CTCF organizes inter-A compartment interactions through RYBP-dependent phase separation

作者：Wei, Chao; Jia, Lumeng; Huang, Xiaona; Tan, Jin; Wang, Mulan; Niu, Jing; Hou, Yingping; Sun, Jun; Zeng, Pengguihang; Wang, Jia; Qing, Li; Ma, Lin; Liu, Xinyi; Tang, Xiuxiao; Li, Fenjie; Jiang, Shaoshuai; Liu, Jingxin; Li, Tingting; Fan, Lili; Sun, Yujie; Gao, Juntao; Li, Cheng; Ding, Junjun

来源：Cell Research, 2022, 32(8): 744-760.

DOI：10.1038/s41422-022-00676-0

• READ ALIGNMENT
• LOOP EXTRUSION
• STRESS GRANULE
• GENOME
• PROTEIN
• COHESIN
• DOMAINS
• PLURIPOTENCY
• PRINCIPLES
• PACKAGE

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.

• 单位
  1; Guangzhou Medical University; Peking University; Southern Medical University; Tsinghua University; Sun Yat-sen University