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Enhancer-promoter interactions and transcription are maintained upon acute loss of CTCF, cohesin, WAPL, and YY1

View ORCID ProfileTsung-Han S. Hsieh, View ORCID ProfileClaudia Cattoglio, View ORCID ProfileElena Slobodyanyuk, View ORCID ProfileAnders S. Hansen, View ORCID ProfileXavier Darzacq, View ORCID ProfileRobert Tjian
doi: https://doi.org/10.1101/2021.07.14.452365
Tsung-Han S. Hsieh
1Department of Molecular and Cell Biology
2Li Ka Shing Center for Biomedical and Health Sciences
3CIRM Center of Excellence
4Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA
6Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA
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  • ORCID record for Tsung-Han S. Hsieh
Claudia Cattoglio
1Department of Molecular and Cell Biology
2Li Ka Shing Center for Biomedical and Health Sciences
3CIRM Center of Excellence
4Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA
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  • ORCID record for Claudia Cattoglio
Elena Slobodyanyuk
1Department of Molecular and Cell Biology
2Li Ka Shing Center for Biomedical and Health Sciences
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  • ORCID record for Elena Slobodyanyuk
Anders S. Hansen
5Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Xavier Darzacq
1Department of Molecular and Cell Biology
2Li Ka Shing Center for Biomedical and Health Sciences
3CIRM Center of Excellence
6Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA
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  • For correspondence: jmlim@berkeley.edu darzacq@berkeley.edu
Robert Tjian
1Department of Molecular and Cell Biology
2Li Ka Shing Center for Biomedical and Health Sciences
3CIRM Center of Excellence
4Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA
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  • For correspondence: jmlim@berkeley.edu darzacq@berkeley.edu
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Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 14, 2021.
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Enhancer-promoter interactions and transcription are maintained upon acute loss of CTCF, cohesin, WAPL, and YY1
Tsung-Han S. Hsieh, Claudia Cattoglio, Elena Slobodyanyuk, Anders S. Hansen, Xavier Darzacq, Robert Tjian
bioRxiv 2021.07.14.452365; doi: https://doi.org/10.1101/2021.07.14.452365
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Enhancer-promoter interactions and transcription are maintained upon acute loss of CTCF, cohesin, WAPL, and YY1
Tsung-Han S. Hsieh, Claudia Cattoglio, Elena Slobodyanyuk, Anders S. Hansen, Xavier Darzacq, Robert Tjian
bioRxiv 2021.07.14.452365; doi: https://doi.org/10.1101/2021.07.14.452365

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