In mammals, early embryos have a unique way of arranging their genes near the nuclear lamina, but the process still needs to be fully understood. Scientists from the Kind Group have discovered new details about DNA organization in early embryo cells. Right after fertilization, each cell can turn into any cell type. The researchers studied how DNA is arranged explicitly during these critical early stages of development.
Although all cells contain the same DNA, they activate only certain parts, resulting in different cell types and functions. This is crucial during early embryo development when each cell can become any type, like brain or placenta cells.
Inside the cell nucleus, DNA is organized into active and inactive regions. The inactive regions are typically more densely packed and less accessible.
Spatial DNA organization is essential because it determines which parts of the DNA are active. This varies between different cell types, such as blood cells and brain cells. In each cell, DNA regions shift their arrangement within the nucleus, turning genes on or off.
These changes shape the cell’s identity and are part of its epigenome, affecting gene activity without changing the DNA itself. While scientists have studied DNA organization in detail, how it is initially established during early embryonic development is still not fully understood.
To better understand embryo development, the researchers aimed to learn how the epigenome regulates DNA organization. In a previous study, the Kind group discovered that DNA regions are unusually positioned near the nuclear edge in the early days of embryo development. This unique arrangement might explain why these early cells can become different types of cells.
Isabel Guerreiro, co-first author of the study, explains: “With this work, we aimed 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 can only collect a few cells from early embryos.”
To study these cells, the researchers used advanced techniques they had previously developed. These methods allowed them to analyze spatial DNA organization in individual early embryo cells.
The scientists employed techniques called scDam&T-seq and EpiDamID to identify DNA regions not near the nuclear edge. They found that these regions have high levels of a specific modification in the proteins around which the DNA is wrapped.
Guerreiro explains, “This suggests this modification repels the DNA regions from the nuclear edge. However, it is not only the presence of this protein modification that decides where DNA regions are located. We found that the balance between the ‘repellent’ 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.”
The researchers discovered a key reason for the unusual spatial DNA organization in the nuclei of early embryo cells. This breakthrough is a significant step toward understanding healthy embryo development and the mechanisms that allow these cells to become various 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.”
Journal Reference:
- Guerreiro, I., Rang, F.J., Kawamura, Y.K. et al. Antagonism between H3K27me3 and genome–lamina association drives atypical spatial genome organization in the totipotent embryo. Nat Genet (2024). DOI: 10.1038/s41588-024-01902-8