Nonequilibrium replication process generates the initial template for chromatin folding.

Abstract

DNA replication is a fundamental process required for duplicating the genome before cell division. However, how epigenetic information is preserved during replication remains poorly understood. DNA replication occurs within specific domains, with replication initiation following a time-regulated pattern. After replication, chromatin must be refolded to restore the 3D structure of the parental chromatin. In this work, we investigate the nonequilibrium problem of how chromatin folds in 3D soon after replication, using stochastic simulation methods, to generate the contact probability map for a specific replicating domain. Our findings indicate that the initial post-replication chromatin structure is influenced by the location of replication origins, the nonequilibrium nature of the replication process, and the speed of the replication fork. Specifically, replication fork speed can significantly impact the organization of newly synthesized chromatin, affecting contact density and enabling the formation of euchromatin-like and heterochromatin-like structures.