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The Mediator complex regulates enhancer-promoter interactions

Shyam Ramasamy, Abrar Aljahani, Magdalena A. Karpinska, T. B. Ngoc Cao, J. Neos Cruz, View ORCID ProfileA. Marieke Oudelaar
doi: https://doi.org/10.1101/2022.06.15.496245
Shyam Ramasamy
1Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
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Abrar Aljahani
1Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
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Magdalena A. Karpinska
1Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
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T. B. Ngoc Cao
1Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
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J. Neos Cruz
1Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
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A. Marieke Oudelaar
1Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
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  • ORCID record for A. Marieke Oudelaar
  • For correspondence: marieke.oudelaar@mpinat.mpg.de
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ABSTRACT

Enhancer-mediated gene activation generally requires physical proximity between enhancers and their target gene promoters. However, the molecular mechanisms by which interactions between enhancers and promoters are formed are not well understood. Here, we investigate the function of the Mediator complex in the regulation of enhancer-promoter interactions, by combining rapid protein depletion and high-resolution MNase-based chromosome conformation capture approaches. We show that depletion of Mediator leads to reduced enhancer-promoter interaction frequencies, which are associated with a strong decrease in gene expression. In addition, we find increased interactions between CTCF-binding sites upon Mediator depletion. These changes in chromatin architecture are associated with a re-distribution of the Cohesin complex on chromatin and a reduction in Cohesin occupancy specifically at enhancers. Our results indicate that enhancer-promoter interactions are dependent on an interplay between the Mediator and Cohesin complexes and provide new insights into the molecular mechanisms by which communication between enhancers and promoters is regulated.

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. All rights reserved. No reuse allowed without permission.
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Posted June 15, 2022.
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The Mediator complex regulates enhancer-promoter interactions
Shyam Ramasamy, Abrar Aljahani, Magdalena A. Karpinska, T. B. Ngoc Cao, J. Neos Cruz, A. Marieke Oudelaar
bioRxiv 2022.06.15.496245; doi: https://doi.org/10.1101/2022.06.15.496245
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The Mediator complex regulates enhancer-promoter interactions
Shyam Ramasamy, Abrar Aljahani, Magdalena A. Karpinska, T. B. Ngoc Cao, J. Neos Cruz, A. Marieke Oudelaar
bioRxiv 2022.06.15.496245; doi: https://doi.org/10.1101/2022.06.15.496245

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