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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. and Peycheva, M. and Rahjouei, A. and Gnan, S. and Klein, K.N. and Nazarova, M. and Schoeberl, U.E. and Gilbert, D.M. and Buonomo, S.C.B. and Di Virgilio, M. and 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
Publisher:Nature Publishing Group
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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