Researchers have discovered an unknown mechanism of how cells ‘remember’ their identity when they divide – the cells’ so-called epigenetic memory.

Nothing lasts forever, and as we age, cells need to replace themselves, which they do by dividing into new cells. However, they don’t make perfect copies of themselves, and during the process of cell division, some information from the ‘mother cell’ is lost.

In the end, cells may have lost so much of the original information that the structure of the genome deteriorates, which makes the new cells less good at their job. They may even do unwarranted thing such as divide too much and become cancer cells.

Longevity.Technology: This information loss over time is damaging to cells, so scientists want to understand more about the mechanism by which cells copy their information in an effort to trigger cells to preserve themselves better and perhaps allow us to slow down aging and or counteract cancer.

Now in a new study, researchers from the University of Copenhagen have discovered a previously-unknown mechanism of how cells ‘remember’ their identity when they divide – the cells’ so-called epigenetic memory.

Publishing in Cell, the researchers detail what they have termed H2A-H2B mediated epigenetic memory [1].

Throughout your life, and driven by environmental and lifestyle factors, your DNA accumulates chemical tags and markers that control which genes are switched on or off and to what degree they are expressed; these tags and markers sit on top of your DNA forming the epigenome. The epigenome alters the way cells read and use the DNA’s instructions. The genetic ingredients stay the same, but the epigenetic recipe book changes over time, as notes are made, steps skipped or added and pages fray and become harder to distinguish.

Each cell type uses a specific combination of information; if a cell accumulates too much wrong or incomplete information, it can lose its function and/or become cancerous. Tags in the epigenome function like bookmarks, ensuring that each cell uses the aforementioned correct combination of information to become the correct cell type.

However, when a cell divides, it is a challenge to introduce these bookmarks fast enough, and the cells’ “identities” can end up eroded, causing aging and cancer. To meet this challenge, the cells uses another type of bookmarks – post-it notes – that act as a fast tracking system keep bookmarks in place and ensure the correct information are used.

This post-it system is what the research team discovered in the new paper, explains Postdoc Valentin Flury, first author of the study.

“We have identified the molecular basis for the post-it notes. Technically speaking, the identified mechanism helps maintain epigenetic cell memory during cell division. We have done it by showing that epigenetic information on histones H2A-H2B is locally and accurately transmitted during DNA replication and, later on, helps to put correct information on histones H3 and H4,” he says.

Flury explains that it is very important for the fields of epigenetics and chromosome replication to realize there are several layers of memory signals that together allow cells to maintain their functionality across cell division.

“It emphasizes the fascinating, complex network acting in each cell of our body to guide development and counteract cancer and aging,” he adds [2].

“Once we fully understand this mechanism, it could help counteract cancer and aging. It is a part of the amazingly complex network acting to maintain function of each cell in our body,” says corresponding author and Professor Anja Groth at the Novo Nordisk Foundation Center for Protein Research.

“If we disrupt this mechanism we could make cells forget their identity and this could help turning them into other cell types which is useful in regenerative medicine.

“Now that we have discovered this new level of regulation, the next step is to understand it in detail and describe its full physiological role. Because before targeting or changing any cellular process, we first need to understand molecularly how it works. Here, we are laying the first bricks on the road to modulate how cells copy the epigenetic landscape. Huge efforts are already being invested in epigenome editing and epigenetic rejuvenation is an emerging hot topic, and our work will feed into these ongoing developments [2].”

[1] https://www.sciencedirect.com/science/article/pii/S0092867423000077
[2] https://healthsciences.ku.dk/newsfaculty-news/2023/02/