Less than 5% of our genome encodes for proteins. However, the remaining fraction of the human genome is not simply formed by “junked” DNA, as previously thought, but it is actually filled with non-coding sequences, called enhancers, that control when, where and how much genes need to be expressed. Consequently, enhancers play major roles during the establishment of gene expression programs as embryonic development takes place. Furthermore, mutations that directly alter enhancers or the communication with their target genes can cause a large number of human diseases, ranging from multiple types of congenital defects to various types of cancer. However, and despite the major functional and medical relevance of enhancers, we still have a limited understanding of the genetic features and mechanisms that enable enhancers to effectively communicate with their target genes. Therefore, revealing the genetic rules and factors that control the communication and compatibility between genes and enhancers would help us to improve the diagnosis, management and even treatment of many human disorders.
The overall goal of our project is to systematically dissect the genetic factors and proteins that control the function of a group of evolutionary conserved enhancers, known as “poised enhancers”, that regulate the expression of major developmental genes. More specifically, we will investigate which proteins allow “poised enhancers” to physically interact with their target genes through the specific 3D organization of the genome in our cells. Moreover, we will also explore the role of a group of DNA sequences known as CpG islands as facilitators of enhancer-gene communication. Overall, our project should provide important insights into the rules governing enhancer-gene communication, which in turn can help us understanding and predicting the pathological consequences of genetic alterations implicated in human disease.
