Mediator recruits the cohesin loader Scc2 to RNA Pol II-transcribed genes and promotes sister chromatid cohesion

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Abstract

The ring-like cohesin complex plays an essential role in chromosome segregation, organization, and double-strand break repair through its ability to bring two DNA double helices together. Scc2 (NIPBL in humans) together with Scc4 functions as the loader of cohesin onto chromosomes. Chromatin adapters such as the RSC complex facilitate the localization of the Scc2-Scc4 cohesin loader. Here, we identify a broad range of Scc2-chromatin protein interactions that are evolutionarily conserved and reveal a role for one complex, Mediator, in the recruitment of the cohesin loader. We identified budding yeast Med14, a subunit of the Mediator complex, as a high copy suppressor of poor growth in Scc2 mutant strains. Physical and genetic interactions between Scc2 and Mediator are functionally substantiated in direct recruitment and cohesion assays. Depletion of Med14 results in defective sister chromatid cohesion and the decreased binding of Scc2 at RNA Pol II-transcribed genes. Previous work has suggested that Mediator, Nipbl, and cohesin connect enhancers and promoters of active mammalian genes. Our studies suggest an evolutionarily conserved fundamental role for Mediator in the direct recruitment of Scc2 to RNA Pol II-transcribed genes.