Cohesin organizes chromatin loops at DNA replication factories

Emmanuelle Guillou; Arkaitz Ibarra; Vincent Coulon; Juan Casado-Vela; Daniel Rico; Ignacio Casal; Etienne Schwob; Ana Losada; Juan Méndez

doi:10.1101/gad.608210

Cohesin organizes chromatin loops at DNA replication factories

¹DNA Replication Group, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain;
²Institut de Génétique Moléculaire de Montpellier, CNRS-Université Montpellier 1 et 2, 34293 Montpellier, Cedex 5, France;
³Protein Technology Unit, Biotechnology Programme, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain;
⁴Structural Computational Biology Group, Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain;
⁵Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain

↵7 Present addresses: Laboratoire de Biologie Moléculaire Eucaryote. 118 Route de Narbonne, 31062 Toulouse, Cedex 9, France;
↵8 Centro Nacional de Biotecnología. Darwin 3, 28049 Madrid, Spain;
↵9 Centro de Investigaciones Biológicas. Ramiro de Maetzu 9, 28040 Madrid, Spain.

↵6 These authors contributed equally to this work.

Abstract

Genomic DNA is packed in chromatin fibers organized in higher-order structures within the interphase nucleus. One level of organization involves the formation of chromatin loops that may provide a favorable environment to processes such as DNA replication, transcription, and repair. However, little is known about the mechanistic basis of this structuration. Here we demonstrate that cohesin participates in the spatial organization of DNA replication factories in human cells. Cohesin is enriched at replication origins and interacts with prereplication complex proteins. Down-regulation of cohesin slows down S-phase progression by limiting the number of active origins and increasing the length of chromatin loops that correspond with replicon units. These results give a new dimension to the role of cohesin in the architectural organization of interphase chromatin, by showing its participation in DNA replication.