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RIF1 regulates early replication timing in murine B cells

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Item Type:Article
Title:RIF1 regulates early replication timing in murine B cells
Creators Name:Malzl, D., Peycheva, M., Rahjouei, A., Gnan, S., Klein, K.N., Nazarova, M., Schoeberl, U.E., Gilbert, D.M., Buonomo, S.C.B., Di Virgilio, M., Neumann, T. and Pavri, R.
Abstract: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.
Keywords:Chromatin, DNA Replication, DNA Replication Timing, Heterochromatin, Mammals, Minichromosome Maintenance Proteins, Replication Origin, Telomere-Binding Proteins, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:14
Number:1
Page Range:8049
Date:11 December 2023
Official Publication:https://doi.org/10.1038/s41467-023-43778-y
PubMed:View item in PubMed

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