Every second, thousands of decisions are made within our cells: which genes to turn on, which to temporarily disable, and which to leave on standby. For a long time, biologists believed that the cell regulated this process quite linearly – simply producing more of the necessary proteins or destroying excess ones. But research published in June 2026 in Nature Cell Biology has shown that nature acts much more subtly.
A team of scientists led by Danfeng Cai from the Johns Hopkins Bloomberg School of Public Health has discovered that one of the key regulators of gene activity – the transcription factor TEAD1 – can exist in two completely different states simultaneously.
The first form consists of small, mobile condensates. This is where the intense work happens: TEAD1 interacts with DNA near enhancers and promoters, initiating gene activity.
The second form turned out to be the complete opposite. These are large condensates located in dense and almost "silent" regions of chromosomes – pericentromeric heterochromatin. Here, TEAD1 does not activate anything. Instead, the cell seemingly sends it to a "storage," where the protein calmly awaits its turn.
This process is based on phase separation – an amazing physical phenomenon that allows proteins to spontaneously assemble into liquid-like droplets without any membranes. In recent years, it has become clear that such condensates are not at all random formations, but one of the main ways of organizing the internal life of the cell. The new work reveals another function: they allow the cell to store a reserve of transcription factors without destroying them and without allowing them to accidentally turn on unnecessary genes.
This mechanism was particularly evident in kidney cancer cells. Researchers found that inactive condensates are about forty times larger than active ones and are particularly numerous in tumor cells with high TEAD1 content. When the formation of these molecular "storage units" was disrupted, the protein became excessively active and triggered the expression of many genes that promote tumor growth. In other words, large condensates act as a kind of fuse, keeping a powerful regulator under control.
At first glance, this work is solely dedicated to oncology. But its significance may be much broader.
TEAD1 is part of the Hippo signaling pathway – one of the most important systems for controlling cell growth, tissue repair, and maintaining cellular equilibrium. Disruptions in this pathway have long been linked not only to tumor development but also to aging processes.
The authors of the study did not directly study aging, but their discovery gives rise to an interesting hypothesis. Perhaps the cell controls gene activity not only by the amount of proteins but also by where exactly they are located within the nucleus. If the ability to create such molecular "pantries" is impaired with age, proteins may end up where they shouldn't be, and genes may be turned on or off at the wrong time. It is known that aging cells gradually lose their ordered nuclear architecture and have poorer control over gene expression. It is possible that failures in the functioning of such condensates are one of the reasons for this process.
Imagine a large library. The most in-demand books are in the reading room – they are constantly taken from the shelves. The rest are carefully stored in the archive and await their turn. If all the books were left in the reading room at once, chaos would quickly ensue. The cell solves this problem in a similar way. Small condensates are "workstations" where TEAD1 turns on genes. Large ones are a well-organized archive that stores a reserve of protein until it is needed again.
This discovery shows that the cell manages its molecular resources much more finely than we imagined just a few years ago. It turns out that for controlling gene activity, not only the amount of regulatory proteins in the nucleus is important, but also where exactly they are located at any given moment. Perhaps the spatial organization of the cell nucleus will become one of the keys to understanding the causes of aging and will help create new strategies for maintaining health, restoring cellular functions, and slowing down age-related changes.
