Cell Reports
Volume 32, Issue 3, 21 July 2020, 107929
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Article
Cohesin-Dependent and -Independent Mechanisms Mediate Chromosomal Contacts between Promoters and Enhancers

https://doi.org/10.1016/j.celrep.2020.107929Get rights and content
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Highlights

  • The majority of promoter-anchored contacts are lost upon rapid degradation of cohesin or CTCF

  • A significant minority of promoter contacts are retained, and some are gained

  • Cohesin-independent promoter contacts preferentially engage active enhancers

  • Loss of cohesin-dependent promoter-enhancer links associates with transcriptional changes

Summary

It is currently assumed that 3D chromosomal organization plays a central role in transcriptional control. However, depletion of cohesin and CTCF affects the steady-state levels of only a minority of transcripts. Here, we use high-resolution Capture Hi-C to interrogate the dynamics of chromosomal contacts of all annotated human gene promoters upon degradation of cohesin and CTCF. We show that a majority of promoter-anchored contacts are lost in these conditions, but many contacts with distinct properties are maintained, and some new ones are gained. The rewiring of contacts between promoters and active enhancers upon cohesin degradation associates with rapid changes in target gene transcription as detected by SLAM sequencing (SLAM-seq). These results provide a mechanistic explanation for the limited, but consistent, effects of cohesin and CTCF depletion on steady-state transcription and suggest the existence of both cohesin-dependent and -independent mechanisms of enhancer-promoter pairing.

Keywords

cohesin
CTCF
promoter capture Hi-C
SLAM-seq
promoter-enhancer interactions
transcriptional regulation

Cited by (0)

7

These authors contributed equally

8

Senior author

9

Present address: Enhanc3D Genomics, Babraham Research Campus, Cambridge CB22 3AT, UK

10

Present address: Institute for Molecular Health Sciences, ETH, 8093 Zurich, Switzerland

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Lead Contact