Affinity-optimizing enhancer variants disrupt development. (https://www.nature.com/articles/s41586-023-06922-8)

These scientists wanted to understand how certain changes in our genes can cause a condition called polydactyly, which means having extra fingers or toes. They focused on a specific part of our genes called enhancers, which control when and where genes are turned on. They found that a particular enhancer called ZRS is important for controlling the growth of fingers and toes.

The scientists discovered that there are some small changes in the ZRS enhancer that are associated with polydactyly. They wanted to figure out how these changes affect the enhancer and cause the condition. They found that these changes make the enhancer bind more tightly to a protein called ETS, which is involved in controlling gene expression.

To study this, the scientists made some changes in the ZRS enhancer in the lab. They created different versions of the enhancer with different levels of binding to the ETS protein. They found that the versions with stronger binding caused more severe forms of polydactyly, with more extra fingers or toes.

They also discovered that similar changes in other enhancers in our genes can cause different conditions, not just polydactyly. These changes make the enhancers bind more tightly to other proteins involved in gene expression.

Overall, the scientists found that small changes in enhancers can have a big impact on how our genes work, leading to different conditions. By studying these changes, scientists can better understand how certain diseases and conditions are caused, and this knowledge can help develop new treatments in the future.

Lim F., Solvason JJ., Ryan GE., Le SH., Jindal GA., Steffen P., Jandu SK., Farley EK. Affinity-optimizing enhancer variants disrupt development. Nature. 2024 Feb;626(7997):151-159. doi: 10.1038/s41586-023-06922-8. Epub 2024 Jan 17.