Enhancer-promoter interactions and transcription are maintained upon acute loss of CTCF, cohesin, WAPL, and YY1
Open accessAbstract
It remains unclear why acute depletion of CTCF and cohesin only marginally affects expression of most genes despite substantially perturbing 3D genome folding at the level of domains and structural loops. To address this conundrum, we used high-resolution Micro-C and nascent transcript profiling to find that enhancer-promoter (E-P) interactions are largely insensitive to acute (3-hour) depletion of CTCF, cohesin, and WAPL. YY1 has been proposed to be a structural regulator of E-P loops, but acute YY1 depletion also had minimal effects on E-P loops, transcription, and 3D genome folding. Strikingly, live-cell single-molecule imaging revealed that cohesin depletion reduced transcription factor binding to chromatin. Thus, although neither CTCF, cohesin, WAPL, nor YY1 are required for the short-term maintenance of most E-P interactions and gene expression, we propose that cohesin may serve as a “transcription factor binding platform” that facilitates transcription factor binding to chromatin.
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Significant numbers of enhancer-promoter contacts remain unaffected upon rapid degradation of cohesin or CTCF, and some contacts even appear de novo.
“Consistent with this, significant numbers of enhancer–promoter contacts remain unaffected upon rapid degradation of these proteins, and some contacts even appear de novo [349, 350].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [350]
The section on loop-extrusion factors reports that approximately 80% of enhancer–promoter contacts remained unaltered after acute CTCF or cohesin depletion. It does not establish that enhancer–promoter contacts appeared de novo after either depletion; the emerging long-range loops it describes followed WAPL depletion and are not identified there as enhancer–promoter contacts. (LLM, conf=0.87)
Experimental — accuracy not yet measuredShort-term YY1 depletion has only a modest effect on enhancer-promoter loops and gene expression.
“(although short-term YY1 depletion has only a modest effect on both [350]).”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [350]
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Aljahani, A., Hua, P., Karpinska, M. A., Quililan, K., Davies, J. O. J., & Oudelaar, A. M. (2022) · Nature Communications · doi:10.1038/s41467-022-29696-5 · Cited by 121 · see citing works
Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
- Authors
- Hsieh, T.-H. S., Cattoglio, C., Slobodyanyuk, E., Hansen, A. S., Darzacq, X., & Tjian, R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Massachusetts Institute of Technology (US)
- University of California, Berkeley (US)
- Corresponding author
- Darzacq, Xavier
- Tjian, Robert
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2021-07-14
- OpenAlex
- W3179929237
- Cited by
- 42
- References
- 23
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 10 · 2022: 16 · 2021: 5
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- enhancer-promoter interactions, CTCF, cohesin, WAPL, YY1, chromatin looping, transcription factor binding, Micro-C, gene expression, chromatin structure
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