In:
Nucleic Acids Research, Oxford University Press (OUP), Vol. 50, No. 1 ( 2022-01-11), p. 207-226
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.
Type of Medium:
Online Resource
ISSN:
0305-1048
,
1362-4962
DOI:
10.1093/nar/gkab1242
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2022
detail.hit.zdb_id:
1472175-2
SSG:
12
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