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CTCF-mediated chromatin looping provides a topological framework for the formation of phase-separated transcriptional condensates

Authors
 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 
Citation
 NUCLEIC ACIDS RESEARCH, Vol.50(1) : 207-226, 2022-01 
Journal Title
NUCLEIC ACIDS RESEARCH
ISSN
 0305-1048 
Issue Date
2022-01
MeSH
CCCTC-Binding Factor / metabolism* ; Cell Cycle Proteins / genetics ; Cell Cycle Proteins / metabolism ; Chromatin / chemistry ; Chromatin / genetics ; Chromatin / metabolism ; Chromatin Assembly and Disassembly* ; Epigenesis, Genetic ; HCT116 Cells ; Humans ; Mediator Complex Subunit 1 / genetics ; Mediator Complex Subunit 1 / metabolism ; RNA Polymerase II / metabolism ; Transcription Factors / genetics ; Transcription Factors / metabolism
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.
Files in This Item:
T202200153.pdf Download
DOI
10.1093/nar/gkab1242
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187866
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