In mammals, only 3% of the genome encodes proteins essential for life and development. However, genes do not operate in isolation; they are regulated by other DNA sequences known as enhancers, which function like switches to turn genes on or off. Researchers at the University of Geneva (UNIGE) have identified 2,700 enhancers that regulate genes involved in bone growth.

Our height is largely inherited, and many genetic diseases impact bone growth. The root cause of these conditions might lie not in the genes themselves, but in the enhancers that activate them. Guillaume Andrey, a researcher at UNIGE, explains that enhancers signal DNA to produce RNA, which in turn synthesizes proteins. While the locations of bone growth genes are known, the specific enhancers controlling them had remained elusive.

Andrey’s team utilized a novel technique to create mouse embryos with fluorescent bones, allowing them to observe enhancer activity during bone development. This method, awarded in 2023, facilitates precise genetic studies using stem cells. The researchers analyzed the activity of chromatin—where DNA is packaged—in fluorescent bone cells, identifying regulatory sequences that control bone-building genes by examining gene activation markers. They confirmed their discoveries by deactivating these enhancers, which resulted in the loss of gene activation, thereby proving the enhancers’ crucial role in proper gene function.

The study identified 2,700 enhancers in mice and found that 2,400 of these are also present in humans. Enhancers and the genes they regulate are located close together on the same DNA strand, enabling efficient interaction, according to Andrey. Variations in the activity of these regions could explain differences in human height, as bone cell activity directly influences bone size.

Many bone diseases cannot be explained solely by gene mutations; the underlying cause may reside in the non-coding regulatory regions of the genome. Some bone diseases are already known to result from mutations in enhancers rather than in the genes themselves, suggesting there could be more such cases, especially when patients’ genes appear normal. Failures in these genetic switches could also lead to other developmental issues, highlighting the importance of enhancers in genetic research and potential treatments.

By Impact Lab