RIF1 regulates early replication timing in murine B cells


  • D. Malzl
  • M. Peycheva
  • A. Rahjouei
  • S. Gnan
  • K.N. Klein
  • M. Nazarova
  • U.E. Schoeberl
  • D.M. Gilbert
  • S.C.B. Buonomo
  • M. Di Virgilio
  • T. Neumann
  • R. Pavri


  • Nature Communications


  • Nat Commun 14 (1): 8049


  • The mammalian DNA replication timing (RT) program is crucial for the proper functioning and integrity of the genome. The best-known mechanism for controlling RT is the suppression of late origins of replication in heterochromatin by RIF1. Here, we report that in antigen-activated, hypermutating murine B lymphocytes, RIF1 binds predominantly to early-replicating active chromatin and promotes early replication, but plays a minor role in regulating replication origin activity, gene expression and genome organization in B cells. Furthermore, we find that RIF1 functions in a complementary and non-epistatic manner with minichromosome maintenance (MCM) proteins to establish early RT signatures genome-wide and, specifically, to ensure the early replication of highly transcribed genes. These findings reveal additional layers of regulation within the B cell RT program, driven by the coordinated activity of RIF1 and MCM proteins.