From the top row, from left, fungi belonging to chytrids and a soil amoeba; from the bottom row, from left, a freshwater amoeba and a ciliate under the microscope. These are the unicellular organisms for which chromatin maps were created for the first time in this study. Image courtesy of Sean Montgomery, Centre for Genomic Regulation (CRG), Barcelona, Spain
Signals used to switch genes on (activate them) in living organisms have remained almost unchanged for 2 billion years, whereas the signals for switching them off (inactivation) have evolved in strikingly different ways across lineages. The findings are expected to provide clues for studying diseases such as cancer that arise when gene control systems malfunction.
A research team led by Arnau Sebé-Pedró at the Centre for Genomic Regulation (CRG) in Barcelona, Spain, compared and analyzed chromatin regulation mechanisms in a wide range of eukaryotes and published their results on the 3rd in the international journal Nature Genetics. Chromatin is a DNA-histone protein complex that resides in the nucleus of eukaryotic cells and plays a role in switching genes on and off, thereby controlling whether genes are expressed.
The study found that “histone tags” attached to the tail regions of histones, the key proteins for gene activation, are similar in almost all eukaryotes, including humans, plants, and amoebae. Histone tags are chemical marks that function like switches to turn genes on.
In contrast, the mechanisms that suppress genes or transposable elements (jumping genes) differed greatly between lineages. This suggests that, since the last common ancestor of eukaryotes, each lineage has evolved its own independent gene repression system. Transposable elements are DNA sequences that can move around to different positions within the genome.
The diversification of gene repression mechanisms is thought to reflect the ongoing conflict between the genome and transposable elements, which are parasitic DNA within the genome. As they hop around, transposable elements can damage genes. When genes are damaged, diseases such as cancer can arise, so transposable elements must be silenced.
The problem is that transposable elements evolve to evade cellular surveillance, for example by acquiring new gene sequences. The team explained that, in order to respond to evolving transposable elements, cells did not rely on a single line of defense but instead evolved a variety of gene repression mechanisms.
For this study, the researchers developed a new analytical method called “iChIP2.” This technology attaches unique molecular barcodes to the chromatin of each species, enabling simultaneous analysis of chromatin from multiple species. It provides an efficient way to compare chromatin states not only in animals such as humans but also in amoebae, algae, fungi, protists, and plants.
Using iChIP2, the team successfully profiled 12 types of histone tags across 12 species. iChIP2 delivered stable analyses using only very small amounts of sample.
The researchers said, “This study is significant because it newly elucidates the evolutionary trajectory of gene regulation in eukaryotes,” adding that “it is expected to offer leads for research into diseases such as cancer that arise from chromatin regulation defects.”
doi.org/10.1038/s41588-026-02672-1
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