The process of DNA replication timing (RT) refers to the specific moments when different regions of our genetic code are duplicated. Researchers from the Institute for Epigenetics and Stem Cells at Helmholtz Munich have implemented a technique called "Repli-seq" to delve into the intimate relationship between RT and the adaptability of cells, the cellular plasticity. Intriguingly, they also uncovered a new relationship between RT and how the genes fold into three-dimensional structures inside the cell nucleus. Starting with the earliest stage of an embryo, the zygote -- the very beginning of an organism's life -- researchers have created a map of RT from this single-cell stage to the stage at which the embryo implants in the mother's womb, called a blastocyst.

 

The unexpected discovery is that the RT in the single-celled embryo is not very ordered, leading to the suggestion that genome duplications are very flexible in these early cells. However, after the 4-cell stage, the RT becomes more defined. There is a gradual process happening, mirroring the gradual acquisition of modifications to the DNA and associated proteins, the so-called chromatin marks, that indicate the genes' activity and importance in the cell's functions. Maria-Elena Torres-Padilla, corresponding author of the study, explains further: "This is remarkable, as this tells us that these early embryo cells have a very 'plastic' genome duplication program. Because these early cells are totipotent, that means, they can create every single cell in our bodies. We think that what we discovered in this study is one of the reasons why these cells are so remarkably capable of generating all the body." The new findings about DNA replication can serve as a tool to reprogram cells.