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The Mediator complex regulates enhancer-promoter interactions

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Ramasamy,  S.
Lise Meitner Group Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Aljahani,  Abrar
Lise Meitner Group Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Karpinska,  Magdalena A.       
Lise Meitner Group Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Cao,  Ngoc Tran Bich
Lise Meitner Group Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Velychko,  Taras       
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Cruz,  J. Neos
Lise Meitner Group Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Lidschreiber,  Michael       
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Oudelaar,  Aukje Marieke       
Lise Meitner Group Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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s41594-023-01027-2.pdf
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Citation

Ramasamy, S., Aljahani, A., Karpinska, M. A., Cao, N. T. B., Velychko, T., Cruz, J. N., et al. (2023). The Mediator complex regulates enhancer-promoter interactions. Nature Structural and Molecular Biology, 30, 991-1000. doi:10.1038/s41594-023-01027-2.


Cite as: https://hdl.handle.net/21.11116/0000-000D-955C-4
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 redistribution of the Cohesin complex on chromatin and a reduction in Cohesin occupancy at enhancers. Together, our results indicate that the Mediator and Cohesin complexes contribute to enhancer-promoter interactions and provide insights into the molecular mechanisms by which communication between enhancers and promoters is regulated.