RIF1 regulates early replication timing in murine B cells

Nat Commun. 2023 Dec 11;14(1):8049. doi: 10.1038/s41467-023-43778-y.


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.

MeSH terms

  • Animals
  • Chromatin / genetics
  • DNA Replication Timing*
  • DNA Replication* / genetics
  • Heterochromatin / genetics
  • Mammals / genetics
  • Mice
  • Minichromosome Maintenance Proteins / metabolism
  • Replication Origin / genetics
  • Telomere-Binding Proteins / metabolism


  • Chromatin
  • Heterochromatin
  • Minichromosome Maintenance Proteins
  • Telomere-Binding Proteins
  • Rif1 protein, mouse