CTCF-mediated chromatin looping provides a topological framework for the formation of phase-separated transcriptional condensates
| Autor: | Ryanggeun Lee, Moo-Koo Kang, Yong-Jin Kim, Bobae Yang, Hwanyong Shim, Sugyung Kim, Kyungwoo Kim, Chul Min Yang, Byeong-gyu Min, Woong-Jae Jung, Eun-Chong Lee, Jung-Sik Joo, Gunhee Park, Won-Ki Cho, Hyoung-Pyo Kim |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Nucleic Acids Research. 50:207-226 |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | CTCF is crucial to the organization of mammalian genomes into loop structures. According to recent studies, the transcription apparatus is compartmentalized and concentrated at super-enhancers to form phase-separated condensates and drive the expression of cell-identity genes. However, it remains unclear whether and how transcriptional condensates are coupled to higher-order chromatin organization. Here, we show that CTCF is essential for RNA polymerase II (Pol II)-mediated chromatin interactions, which occur as hyperconnected spatial clusters at super-enhancers. We also demonstrate that CTCF clustering, unlike Pol II clustering, is independent of liquid-liquid phase-separation and resistant to perturbation of transcription. Interestingly, clusters of Pol II, BRD4, and MED1 were found to dissolve upon CTCF depletion, but were reinstated upon restoration of CTCF, suggesting a potent instructive function for CTCF in the formation of transcriptional condensates. Overall, we provide evidence suggesting that CTCF-mediated chromatin looping acts as an architectural prerequisite for the assembly of phase-separated transcriptional condensates. |
| Databáze: | OpenAIRE |
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