New insights into DNA organization during embryonic development

Every cell in our body contains the same DNA. This DNA contains the genetic information that serves as a blueprint for making the proteins necessary for the cell to function. Although all cells have the same DNA, they only activate specific parts of it. As a result, cells develop into different cell types and perform different functions. This is especially relevant during embryo development. When the embryo first forms after fertilization, any cell can become any type of cell, including brain cells or even placenta cells.

DNA organization in the nucleus

DNA is located in the cell nucleus, where it is folded into active and inactive compartments. Regions of DNA located at the edge of the cell nucleus are normally more densely packed and inactive. This spatial DNA organization is important because it determines which parts of the DNA are active. This differs per cell type, for example between blood cells and brain cells. In cells with different functions, specific regions of DNA change their packaging and spatial organization within the nucleus. This results in various genes being switched ‘off’ and ‘on’. These changes determine which genes are active and give the cell its identity. Such processes that affect the activity of genes without changing the DNA itself form the epigenome of the cell. Although scientists have extensively investigated the spatial organization of DNA, much remains unclear about how this organization is first established during embryonic development.

Unique DNA organization in early embryos

To better understand embryo development, the researchers wanted to know how the epigenome regulates the organization of DNA. In a previous study, researchers from the Kind group showed that the positioning of DNA regions near the nuclear edge during the first days of embryo development is highly unusual during early embryo development. This could explain how those first cells can be so flexible in what they can become. Isabel Guerreiro, co-first author of the study, explains: ‘With this work, we wanted to understand what causes the unusual positioning of DNA regions at the edge of the nucleus during early mammalian development. This is often difficult to study because we collect only a few cells from early embryos.” To study these cells, the researchers used techniques they had previously developed. With these techniques, they were able to examine the spatial DNA organization in individual cells from early analyze embryos.

Causes of unique DNA organization in early embryos

Using these techniques, called scDam&T-seq and EpiDamID, the researchers found that regions of DNA that are not near the nuclear edge have high levels of specific modification in the proteins the DNA is wrapped around. “This suggests that the presence of this modification repels the DNA regions from the nuclear edge,” Guerreiro explains. “However, it is not just the presence of this protein modification that determines where DNA regions are located. We found that the balance between the ‘repulsive’ protein modification and an intrinsic attraction of the DNA sequence to the nuclear edge determines the unusual organization. of DNA regions in the cell nucleus of early embryos.”

Understanding embryo development

The researchers have found an important cause for the atypical spatial DNA organization in the nucleus of early embryo cells. These findings represent an important step toward understanding the development of healthy embryos and uncovering the mechanisms that allow these cells to differentiate into a wide variety of cell types. Guerreiro says: “Uncovering the mechanism behind the unusual nuclear organization that characterizes the early embryo has the potential to improve regenerative medicine strategies and human in vitro fertilization outcomes.”