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RIF1 regulates replication origin activity and early replication timing in B cells
- Publication Year :
- 2023
- Publisher :
- Cold Spring Harbor Laboratory, 2023.
-
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 B lymphocytes, RIF1 binds predominantly to early-replicating active chromatin, regulates early origin firing and promotes early replication. RIF1 has a minor role in 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 new layers of regulation within the B cell RT program, driven by the coordinated activity of RIF1 and MCM proteins.
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi...........0ca2f9f2410fc9104796be93eee4e079