Journal
CELL RESEARCH
Volume 32, Issue 8, Pages 744-760Publisher
SPRINGERNATURE
DOI: 10.1038/s41422-022-00676-0
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Funding
- National Key RD Program [2017YFA0102800]
- National Natural Science Foundation of China [81890991, 31970811, 31771639, 32170798, 31900519]
- Guangdong Regenerative Medicine and Health of Guangdong Laboratory Frontier Exploration Project [2018GZR110105007]
- Guangdong Innovative and Entrepreneurial Research Team Program [2016ZT06S029]
- Guangdong Basic and Applied Basic Research Foundation [2021B1515120063]
- Fundamental Research Funds for the Central Universities of Jinan University [116210004]
- China Postdoctoral Science Foundation [55350600]
- Natural Science Foundation of Guangdong Province, China [2021A1515010938]
- Natural Science Foundation of China [32025006, 31871266]
- National Key R&D Program of China [2021YFA1100300, 2016YFA0100103]
- State Key R&D Program of China [2017YFA0505503]
- CAS Interdisciplinary Innovation Team [JCTD-2020-04]
- Beijing Municipal Natural Science Foundation [Z200021]
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This study reveals a novel role of CTCF in organizing long-range chromatin interactions, where CTCF phase separation mediated by RYBP promotes inter-A compartment interactions and enhances the self-renewal ability of embryonic stem cells.
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.
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