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Enhancer-promoter contact formation requires RNAPII and antagonizes loop extrusion

Shu Zhang, Nadine Übelmesser, Mariano Barbieri, View ORCID ProfileArgyris Papantonis
doi: https://doi.org/10.1101/2022.07.04.498738
Shu Zhang
1Institute of Pathology, University Medical Center Göttingen, 37075 Göttingen, Germany
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Nadine Übelmesser
1Institute of Pathology, University Medical Center Göttingen, 37075 Göttingen, Germany
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Mariano Barbieri
1Institute of Pathology, University Medical Center Göttingen, 37075 Göttingen, Germany
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Argyris Papantonis
1Institute of Pathology, University Medical Center Göttingen, 37075 Göttingen, Germany
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  • ORCID record for Argyris Papantonis
  • For correspondence: argyris.papantonis@med.uni-goettingen.de
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SUMMARY

Mammalian chromosomes are folded by converging and opposing forces. Here, we tested the role of RNAPII across different scales of interphase chromatin folding in a cellular system allowing for its auxin-mediated degradation. We used Micro-C and computational modeling to characterize subsets of loops differentially gained or lost upon RNAPII depletion. Gained loops, extrusion of which was antagonized by RNAPII, almost invariably formed by engaging new or rewired CTCF anchors. Lost loops selectively concerned contacts between enhancers and promoters anchored by RNAPII. Surprisingly, promoter-promoter contacts were almost insensitive to polymerase depletion and sustained cohesin occupancy in its absence. Selective loss of enhancer-promoter contacts explains the repression of most genes. Together, our findings reconcile the role of RNAPII in transcription with that in setting-up regulatory 3D chromatin architectures genome-wide, while also revealing a direct impact on cohesin loop extrusion.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
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 04, 2022.
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Enhancer-promoter contact formation requires RNAPII and antagonizes loop extrusion
Shu Zhang, Nadine Übelmesser, Mariano Barbieri, Argyris Papantonis
bioRxiv 2022.07.04.498738; doi: https://doi.org/10.1101/2022.07.04.498738
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Enhancer-promoter contact formation requires RNAPII and antagonizes loop extrusion
Shu Zhang, Nadine Übelmesser, Mariano Barbieri, Argyris Papantonis
bioRxiv 2022.07.04.498738; doi: https://doi.org/10.1101/2022.07.04.498738

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