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Item Type: | Article |
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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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