Scientists Solve ‘Mystery Through the Ages’

The upper panel shows a configuration other than Rabl. Centromeres in magenta, dispersed in nuclei in green. The bottom panel shows the Rabl configuration. Centromeres are unevenly distributed in the nuclei. Credit: Sachihiro Matsunaga, University of Tokyo

Biologists uncover a mechanism that shapes the distribution of centromeres.

Since the 1800s, scientists have noticed the configuration of centromeres, a special chromosomal region that is vital for cell division, in the cell nucleus. However, until now the determining mechanisms and biological significance of centromere distribution were poorly understood. Recently, researchers proposed a two-step regulatory mechanism that shapes the distribution of centromeres. Their findings also indicate that centromeric configuration in the nucleus plays a role in maintaining genome integrity.

The results were published today (August 1, 2022) in the journal Natural plants. The study was led by researchers from the University of Tokyo and their collaborators.

Special chromosomal domains known as centromeres are drawn to opposite ends of the cell during the process of cell division. After the completion of cell division and the construction of the cell nucleus, the centromeres are spatially distributed in the nucleus. If the distribution of centromeres drawn to both poles remains unchanged, the cell nucleus will have centromeres clustered on only one side of the nucleus. This uneven distribution of centromeres is called the Rabl configuration, after Carl Rabl, a 19th-century cytologist. Instead, the nuclei of some species show a scattered distribution of centromeres. This is known as the Rabl-free configuration.

“The biological function and molecular mechanism of the Rabl or non-Rabl configuration has been a mystery for centuries,” said corresponding author Sachihiro Matsunaga, a professor at Tokyo University of Frontier Sciences. “We have successfully revealed the molecular mechanism for constructing a non-Rabl configuration.”

Distribution of centromeres in the root

The uneven distribution of centromeres (magenta) in the nuclei (green). Credit: Sachihiro Matsunaga, University of Tokyo

Scientists studied the plant Arabidopsis thaliana, also known as thale cress and a specimen known to have a non-Rabl configuration, and its mutant form which has a Rabl configuration. Through their work, they discovered that protein complexes known as condensin II (CII) and protein complexes known as linker of the nucleoskeleton and catoskeleton complex (LINC) work together to determine the distribution of centromeres during cell division.

“Centromere distribution for the non-Rabl configuration is independently regulated by the CII–LINC complex and a nuclear lamina protein known as CROWDED NUCLEI (CRWN),” Matsunaga said.

The first step in the two-step regulatory mechanism of centromere distribution that the researchers discovered was that the CII-LINC complex mediates the dispersion of centromeres from late anaphase to telophase, two phases at the end of cell division. The second step in the process is that CRWNs stabilize the scattered centromeres on the nuclear lamina in the nucleus.

Next, to investigate the biological significance, the researchers analyzed gene expression in A. thaliana and in its Rabl-structural mutant. Because the change in the spatial arrangement of centromeres also changes the spatial arrangement of genes, the researchers expected to find differences in gene expression, but this hypothesis turned out to be incorrect. However, when[{” attribute=””>DNA damage stress was applied, the mutant grew organs at a slower rate than the normal plant.

“This suggests that precise control of centromere spatial arrangement is required for organ growth in response to DNA damage stress, and there is no difference in tolerance to DNA damage stress between organisms with the non-Rabl and Rabl,” Matsunaga said. “This suggests that the appropriate spatial arrangement of DNA in the nucleus regardless of Rabl configuration is important for stress response.”

According to Matsunaga, the next steps are to identify the power source that changes the spatial arrangement of specific DNA regions and the mechanism that recognizes specific DNA.

“Such findings will lead to the development of technology for artificially arranging DNA in the cell nucleus in an appropriate spatial arrangement,” he said. “It is expected that this technology will make it possible to create stress-resistant organisms, as well as to impart new properties and functions by altering the spatial arrangement of DNA rather than editing its nucleotide sequence.”

Reference: “Two-step regulation of centromere distribution by condensin II and the nuclear envelope proteins” by Takuya Sakamoto, Yuki Sakamoto, Stefan Grob, Daniel Slane, Tomoe Yamashita, Nanami Ito, Yuka Oko, Tomoya Sugiyama, Takumi Higaki, Seiichiro Hasezawa, Maho Tanaka, Akihiro Matsui, Motoaki Seki, Takamasa Suzuki, Ueli Grossniklaus and Sachihiro Matsunaga, 1 August 2022, Nature Plants.
DOI: 10.1038/s41477-022-01200-3

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