Reprogramming of cell’s genetic information makes way for future cells

The precise times at which certain sections of our genetic code are replicated are called DNA replication timing or RT.

Existence is passed from one cell to the next and from one creature to the next by the complex process of copying genetic information, often known as DNA replication. This is accomplished by more than merely duplicating the genetic code; a precise timing of a well-planned series of molecular activities is required. Researchers working with Prof. Maria-Elena Torres-Padilla of Helmholtz Munich have recently discovered an intriguing feature of this process called “replication timing” (RT), and how unique this is when life begins.

The findings were published in the Nature Journal.

The precise times at which certain sections of our genetic code are replicated are called DNA replication timing or RT. Utilizing a method known as “Repli-seq,” researchers from the Helmholtz Munich Institute for Epigenetics and Stem Cells have explored the close connection between RT and cellular plasticity, or the capacity of cells to adapt. Interestingly, scientists also found a novel connection between RT and the three-dimensional shapes the genes fold into inside the cell nucleus.

Researchers have made a map of RT from the earliest stage of an embryo, known as the zygote, which is the beginning of an organism’s existence, to the blastocyst, the stage at which the embryo implants in the mother’s womb. The surprising finding that the single-celled embryo’s RT is not well organized raises the possibility that genomic duplications in these early cells are very malleable. Nevertheless, the RT becomes more distinct after the 4-cell stage. A slow process is taking place, similar to the slow accumulation of chromatin marks on DNA and related proteins that signify the activity of a gene and its significance for cellular processes.

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his 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.

Maria-Elena Torres-Padilla

The new findings about DNA replication can serve as a tool to reprogram cells.

We can envision changing the cell identity by changing its RT program into a more flexible one.

Dr. Tsunetoshi Nakatani

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The results further demonstrate that RNA polymerase the enzyme that reads genetic code and converts it into RNA contributes to identifying the precise RT program and offers some guidance on how to modify it in the future. The study team has shown that the RT program is created when the three-dimensional structure of the genome takes shape. This is a fascinating discovery because it suggests that the flexibility of the RT program is influenced by how our genome fits into the three-dimensional space of the cell nucleus.

To sum up, the time of DNA replication is an intriguing aspect of the whole story of life. It illustrates how the ability of cells from the early embryo to produce different cell types in our body is closely linked to the accuracy of genetic replication. We learn more about the fundamentals of life’s transmission from organism to organism and cell to cell, as well as what allows a cell to be able to create a new body, as researchers delve deeper into these linkages.

Source: Helmholtz Munich News

Journal Reference: Nakatani, T., Schauer, T., Klein, K. N., Ettinger, A., Pal, M., & Gilbert, D. M. (2023). Emergence of replication timing during early mammalian development. Nature, 1-9.

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