RIF1 regulates early replication timing in murine B cells

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.; Pavri, R.

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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