DNA replication in early mammalian embryos is patterned, predisposing lamina-associated regions to fragility
Year: 2024
Type: article
Abstract: DNA replication in differentiated cells follows a defined program, but when and how it is established during mammalian development is not known. Here we show using single-cell sequencing, that both bovine and mouse cleavage stage embryos progress through S-phase in a defined pattern. Late replicating regions are associated with the nuclear lamina from the first cell cycle after fertilization, and contain few active origins, and few but long genes. Chromosome breaks, which form spontaneously in bovine embryos at sites concordant with human embryos, preferentially locate to late replicating regions. In mice, late replicating regions show enhanced fragility due to a sparsity of dormant origins that can be activated under conditions of replication stress. This pattern predisposes regions with long neuronal genes to fragility and genetic change prior to segregation of soma and germ line. Our studies show that the formation of early and late replicating regions is among the first layers of epigenetic regulation established on the mammalian genome after fertilization.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: U.S. Department of Health and Human Services, U.S. Department of Agriculture, Memorial Sloan-Kettering Cancer Center, New York State Stem Cell Science, National Institutes of Health, National Institute of Food and Agriculture, Agricultural Research Service, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1190388083, DNA repair pathway choice mediates somatic cell reprogramming, G2347758286, DNA Methylation at N6-Adenine in Placental Trophoblast Development, G329294694, G5846184781, Novel approaches to map DNA replication traffic in a genome-wide scale, G7977794829, G814104610, G814399200, The Genetic Basis of Human DNA Replication Timing, Causes and Consequences of DNA Replication Stress in the Mammalian Preimplantation Embryo
OpenAlex ID: W4399806610