The Mediator complex regulates enhancer-promoter interactions.

Autor: Ramasamy S; Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Aljahani A; Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Karpinska MA; Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Cao TBN; Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Velychko T; Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Cruz JN; Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Lidschreiber M; Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Oudelaar AM; Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany. marieke.oudelaar@mpinat.mpg.de.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2023 Jul; Vol. 30 (7), pp. 991-1000. Date of Electronic Publication: 2023 Jul 10.
DOI: 10.1038/s41594-023-01027-2
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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