Scientists have long been curious about a mysterious part of our DNA called heterochromatin, often called the “dark side of the genome.”
This area makes up about half of our genetic material, yet it has remained largely unexplored—until now.
Inside heterochromatin are pieces of DNA called transposable elements (TEs), sometimes nicknamed “jumping genes.”
These genes are normally silent and buried deep in the DNA, but under certain conditions, they can “wake up” and even jump into other parts of our genome.
This can cause problems—but also, in rare cases, help with evolution. For example, some TEs helped create important genes in our immune system and during the development of the placenta in mammals.
But in general, when these jumping genes are activated at the wrong time or place, they can lead to serious health issues. Scientists have linked TE activity to aging, cancer, and autoimmune diseases. That’s why keeping them in check is so important.
A new study led by Professor Anjana Rao at the La Jolla Institute for Immunology has found a key player in this process: an enzyme called O-GlcNAc transferase (OGT).
This enzyme helps cells control the activity of TEs and keep them quiet, which is crucial for maintaining healthy cells.
Think of heterochromatin as a prison that locks away these dangerous genes. OGT helps maintain that prison. Without OGT, the prison doors start to open, and the jumping genes can escape and cause damage.
The study also looked at another group of proteins called TET enzymes, which OGT works closely with.
TETs help turn genes on and off by modifying the chemical markers on DNA. These markers—called 5mC (which silences genes) and 5hmC (which activates them)—allow cells to respond to changes in their environment. But when TET proteins are not properly controlled, they can accidentally switch on too many genes, including the TEs.
Using advanced DNA sequencing technologies, including a powerful method called duet evoC, the researchers discovered that OGT helps limit TET activity in the parts of the genome where TEs are hidden.
By doing so, OGT prevents the wrong genes from being activated.
This discovery could be important for future treatments of diseases like cancer and autoimmune disorders. If scientists can find a way to control OGT or TET activity, they might be able to stop dangerous genes from causing harm.
As researcher Dr. Hugo Sepulveda explained, cells constantly work hard to keep these jumping genes silent.
Understanding how this happens gives scientists new tools to explore disease and possibly create better therapies.
The next step is to learn even more about how OGT works and how problems with this system may contribute to disease. But for now, it’s clear that this one enzyme plays a powerful role in keeping our DNA—and our health—in check.
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