16.11.2020 change 16.11.2020

How do cells memorize information? A new lead

Figure: Graph shows how transcriptional memory works. When cells are first exposed to gamma interferon, gene expression is observed. When the stimulus reoccurs two weeks later, there are genes whose expression is stronger. Dr. Siwek investigated the mechanisms leading to such stronger expression. Credit: Wojciech Siwek Figure: Graph shows how transcriptional memory works. When cells are first exposed to gamma interferon, gene expression is observed. When the stimulus reoccurs two weeks later, there are genes whose expression is stronger. Dr. Siwek investigated the mechanisms leading to such stronger expression. Credit: Wojciech Siwek

How is the information about the stimuli the cell came into contact with recorded in its genome? There are still many unknowns, but a new lead comes from research conducted by a Polish scientist: cohesin, the protein 'clip' of the genome may be involved.

Memory is associated mainly with the work of the brain, i.e. neurons. The process of remembering and storing information is also extremely important for the work of the immune system, the task of which is to fight infections. But many other cells in the body must register and learn to respond to stimuli as well.

But where is the memory actually located at the level of individual cells and compounds? There is still no complete answer to this question.

An element of research on how organisms store information is research on transcriptional (cell) memory. When exposed to external signals, a cell can activate specific genes and start producing specific proteins. The information about the cell's response to a given signal is somehow recorded in the genome, not by changes in the DNA sequence, but, for example, by epigenetic changes, such as spatial changes in the arrangement of genetic material, the way it is folded. Thanks to this, when a given signal occurs again, the cell can respond more effectively.

Dr. Wojciech Siwek from the University of Oxford said: “We did not know what exactly was responsible for transcriptional memory. I tested some 50 different hypotheses. None was confirmed.” But patience paid off, and the scientist finally found an important lead. His research shows that a certain protein called cohesin must be associated with transcriptional memory. The research appeared in Molecular Cell (https://doi.org/10.1016/j.molcel.2020.10.005)

Cohesin forms a ring-like structure, with which the genome is folded. It has a huge role especially during cell division, when DNA strands have to fold into neat, tightly packed chromosomes. However, cohesin also works at other times in the cell's life. It is responsible for genome folding and regulation of gene expression.

Dr. Siwek studied the response of cancer cells (HeLa) and skin cells to a repeated stimulus. First, the cells were exposed to gamma interferon, a protein secreted, for example, during viral infections. And then, after several days, this signal was repeated.

Researchers observed that certain genes responded with a much more intense protein production on the second exposure than on the first. The stronger response was noticeable even after 14 days, when the cells had already gone through about 14 division cycles. The information about the reaction to interferon had to be not only stored in cells that had direct contact with the stimulus, but also transmitted through mitotic divisions.

Scientists identified the gene that differed most in expression when re-exposed to interferon. They investigated what determined the differences in its expression. It turned out that cohesion was important. Its local removal from the space around the gene significantly improved the cell's response to the signal.

The research does not yet answer the question of how cohesin affects the memory of signals, but we now known that it is involved.

Dr. Siwek said: “If we could learn to influence and modify transcriptional memory, perhaps a therapy based on cellular memory would become real in the distant future. And we could develop more effective ways to combat cyclical infections, such as the influenza virus, or develop new ways to prevent disease recurrence of cancer.”

PAP - Science in Poland, Ludwika Tomala

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