Tea Toteva, Bethany Mason, Yutaka Kanoh, Peter Brøgger, Daniel Green, Janne Verhein-Hansen, Hisao Masai, and Geneviève Thona,

PNAS January 31, 2017. 114 (5) 1093-1098

In recent years, high-throughput studies have revealed the organization of eukaryotic genomes into chromatin domains, topologically associated domains, and replication domains, laying out important principles for the spatiotemporal organization of the nucleus. Our work shows how customized genetic screens with model organisms can help delineate functional relationships between the different layers of organization and identify the cis- and trans-acting elements underpinning them. Here, such approaches revealed that DNA elements and proteins that regulate replication-origin firing in yeasts and other eukaryotes can help partition the genome into expressed and repressed domains. We expect this insight acquired with fission yeast will inspire research in other organisms where the proteins we identified, the Shelterin component Rif1 and its effectors, are intensively studied.