July 8, 2026

How cells keep genomic hitchhikers under control

Much of the genome is made up of repetitive DNA sequences that trace back to ancient mobile elements, many of which have lost their ability to copy themselves into new locations but can still cause problems if they become active again at the wrong time. Now, two studies from FMI scientists reveal how cells keep these potentially disruptive genetic elements under control. The researchers found that a protein complex called ChAHP acts as a targeted genome-defense system, preventing the transcription machinery from switching on these elements in mouse cells. The findings offer insight into how cells manage repetitive sequences while protecting genome stability.

Much of our genome is made up of DNA sequences that once had the ability to copy and paste themselves into new locations. These elements, known as transposons, have helped shape evolution, but they can also threaten genome stability if they become active at the wrong time.

In two complementary studies, researchers in the group of Marc Bühler have uncovered how cells keep one class of these elements under control. The work focuses on SINEs, short repetitive DNA sequences scattered throughout the genome that can be extremely abundant; human DNA, for example, contains more than 1 million copies of one type of SINE.

Although SINEs do not encode proteins, some can still be copied into RNA by the cell’s transcription machinery, creating the potential for genomic disruption.

The researchers found that a protein complex called ChAHP acts as a molecular guard by preventing the cell’s transcription machinery from switching on a potentially disruptive group of mouse SINEs known as SINE B2 elements.

One study showed that ChAHP blocks the recruitment of a key factor required for the transcription machinery to begin transcription of SINE B2 elements.

The second study revealed how ChAHP carries out this repression: A component of the complex restricts access to SINE B2 elements through the remodeling of chromatin — the tightly organized package of DNA and proteins inside the cell nucleus.

Controlling repetitive elements with precision may be important for SINEs because they are often located near genes, where broad silencing mechanisms could have unwanted effects, the researchers say.

Together, they add, the findings reveal a targeted genome-defense strategy and shed light on how cells manage the many repetitive sequences embedded in our DNA.