The team discovered a relationship between the timing of DNA replication and how genes fold into 3D structures within the cell nucleus

RT emerges gradually during mouse preimplantation development. aOverview of single-cell Repli-seq used to generate RT profiles from single cells of mouse preimplantation embryos based on copy number variation. b, Schematic of the sampling of embryos and corresponding images of dissociated blastomeres at each stage. The number of independent blastomere collections for each stage with similar results is as follows: zygote (3), 2-cell (4), 4-cell (3), 8-cell (3), 16 -cell (3), morula (2), ICM (4). Scale bar, 50m. c, Heatmaps of single cells showing replication status based on binarized copy number during preimplantation embryogenesis (red, replicated; gray, not replicated). Cells are ranked by their percentage of replicated genome (replication score), which indicates S phase progression and is plotted as a bar plot on the left. d, Variability score during embryonic development; the score is 1 when 50% of cells replicated in the genomic bin and 0 when all cells are either replicated (100%) or non-replicated (0%). Each violin plot shows the distribution of scores for all genomic bins. eRT profiles of preimplantation embryos over a representative region of chromosome2, indicated by the black rectangle in c. The black line indicates the RT profiles, calculated as the average of the overlapping intervals defined by the genome-wide replication score. f,gSize (f) and number (g) of replication have RT peaks (also known as initiation zones), and RT troughs (also known as termination zones) during preimplantation development. The box plots show the median and interquartile range (IQR), and the whiskers depict the lowest and highest values ​​within 1.5IQR. bp, base pair. h, Relative RT values ​​centered on RT peaks during embryonic development compared to their neighboring regions. Note that the curves for the 2- and 4-cell stages overlap and, to some extent, those of the zygotes. Credit: NATURE (2023). DOI: 10.1038/s41586-023-06872-1

The intricate process of duplicating genetic information, called DNA replication, is at the heart of the transmission of life from one cell to another and from one organism to the next. This happens by not only copying the genetic information; a well-ordered sequence of molecular events must also occur at the right time.

Scientists working with Prof. Maria-Elena Torres-Padilla from Helmholtz Munich recently discovered a fascinating aspect of this process known as “replication timing” (RT) and how special it is when life begins. The new results are now published in the NATURE.

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 in Helmholtz Munich implemented a technique called “Repli-seq” to investigate the close relationship between RT and the adaptability of cells, the cellular plasticity.

Interestingly, they also discovered a new relationship between RT and how genes fold into three-dimensional structures inside the cell nucleus.

Starting from the earliest stage of an embryo, the zygote, the beginning of an organism’s life, researchers have created an RT map from this single-cell stage to the stage where the embryo implants in the mother’s womb, which called a blastocyst. An unexpected discovery was that RT in single-celled embryos was not highly ordered, suggesting that genome duplications are very flexible in these early cells.

However, after the 4-cell stage, RT becomes more pronounced. A gradual process is taking place, reflecting the gradual acquisition of changes in DNA and associated proteins, the so-called chromatin marks, which indicate the activity of genes and the importance of functions in the cell.

Maria-Elena Torres-Padilla, corresponding author of the study, explains further, “This is remarkable, because it tells us that these early embryonic cells have a ‘plastic’ program to duplicate the genome . Since these first cells are totipotent, they can make every single cell in our bodies. We believe that what we discovered in this study is one of the reasons why these cells are so unique that they are able to create all the bodies. “

New findings about DNA replication could be a tool to reprogram cells. Dr. Tsunetoshi Nakatani, the first author of the study, added, “We can imagine changing the identity of the cell by changing its RT program to be more flexible.”

The results also show that RNA polymerase, commonly known as the enzyme responsible for reading the genetic code and transcribing it into RNA, contributes to determining the exact program of RT, providing some clues as to whether how to be able to manipulate that program in the future. .

The research team discovered that the three-dimensional structure of the genome was formed first, and the RT program was established because of this. This is an exciting finding, because it posits that how our genome is accommodated in the three-dimensional space of the cell nucleus influences the flexibility of the RT program.

In conclusion, the timing of DNA replication is a fascinating puzzle piece in the grand narrative of life. It shows how the accuracy of genetic replication is closely tied to the capacity of cells from the early embryo to generate other cell types in our body. As researchers continue to explore these connections, we gain a deeper understanding of the essence of life transmission, cell to cell, organism to organism, and what enables a cell to produce new body.

More information:
Maria-Elena Torres-Padilla, Evolution of the timing of reproduction during early mammalian development, NATURE (2023). DOI: 10.1038/s41586-023-06872-1

Provided by the Helmholtz Association of German Research Centers

Citation: Team discovers relationship between timing of DNA replication and how genes fold into 3D structures inside cell nucleus (2023, December 20) retrieved on December 21, 2023 from https://phys .org/news/2023-12-team-relationship-dna-replication-genes.html

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