Mediator Recruits the Cohesin Loader Scc2 to RNA Pol II Transcribed Genes and Promotes Sister Chromatid Cohesion

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 function as the loader of cohesin onto chromosomes. The RSC complex has been shown to act as a chromatin adapter, facilitating localization of the Scc2-Scc4 cohesin loader. Here we identify a broad range of Scc2- chromatin protein interactions that are evolutionarily conserved, consistent with a multifactorial adaptor landscape. We reveal a role for one complex, Mediator, in recruitment of the cohesin loader. Med14, a subunit of the Mediator complex, is a high copy suppressor of Scc2 mutants. Physical and genetic interactions between Scc2 and Mediator are functionally substantiated in direct recruitment and cohesion assays. Mediator can provide recruitment function for Scc2 based on a chromatin tethering experiment. Depletion of Med14 results in defective sister chromatid cohesion and 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 in yeast suggest an evolutionarily conserved fundamental role for Mediator in direct recruitment of Scc2 to RNA pol II transcribed genes.