한빛사 논문
Ryanggeun Lee1,2,†, Moo-Koo Kang3,4,†, Yong-Jin Kim3,4,†, Bobae Yang3,4,†, Hwanyong Shim1,†, Sugyung Kim3,4, Kyungwoo Kim3,4, Chul Min Yang3, Byeong-gyu Min1, Woong-Jae Jung3, Eun-Chong Lee3, Jung-Sik Joo3,4, Gunhee Park1, Won-Ki Cho1,5,* and Hyoung-Pyo Kim3,4,6,*
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea, 2College of Natural Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea, 3Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea, 4Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea, 5KI for Health Science and Technology (KIHST), Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea and 6Yonsei Genome Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
*To whom correspondence should be addressed.
†The authors wish it to be known that, in their opinion, the first five authors should be regarded as Joint First Authors.
Abstract
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.
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