In our body, the genes are not all active at the same time. Their activation is finely controlled to ensure the proper functioning of our cells. This control is exercised by specific DNA regions, called regulatory elements. When these regions are altered, this can disrupt the activity of genes and contribute to the development of diseases such as cancers, neurological disorders or even malaria.
Step: a new dual -function regulator element in immune cells
In a study conducted on factors of susceptibility to the serious forms of malaria and published in the journal Cell Genomicsscientists have discovered a new type of regulatory element, baptized to Spiromoter.
This regulatory region has a unique double function in T immune cells, which play a central role in defense against infections.
- It activates the expression of the gene ATP2B4 (Role of enhancer),
- And at the same time, it slows down the expression of the gene Lax1 (role of silencer),
in the same cell.
These two genes are important for the regulation of two essential biological functions that are the homeostasis of calcium and the activation of immune cells T.
When scientists abolish this espromoter region by modifying the genome, the first gene (ATP2B4) becomes less active while the second (Lax1) is more expressed. This prevents activation of T cells, which can alter the immune response.
Discreet genetic variations with powerful effects
But that’s not all, scientists also spotted a small genetic variation named rs11240391, located in the promoter of the gene Lax1. This variant, which often goes unnoticed in major genetic studies has a strong impact. In combination with variations in the espromoter, it increases the risk of developing a serious form of malaria and leads to an excessive decrease in the expression of the gene Lax1, resulting in hyperactivation of T cells.
Thanks to an approach combining genetic, bio-informational and experimental studies, scientists have been able to better identify hidden regulatory elements and their impacts on complex diseases such as malaria. This work opens the way to better taking into account non-coding variations in our DNA, often overlooked, but which can play a decisive role in our health.