Regulation of gene expression in eukaryotes involves complex networks of proteins. DNA-binding transcription factors are an important component of these networks. Transcription factors are vital for the normal development of an organism, as well as for routine cellular functions and response to disease. They can activate or repress the transcription of a gene, which is generally a key determinant for gene functions at a given time. Transcription factors are known to recruit intermediary proteins such as cofactors to modulate activities.
Nowadays, it is possible to describe the components which are able to initiate the gene transcription. However, there is a lack of knowledge about how these elements interact with each other. Our approach is based on the determination of complexes formed by transcription factors as fundamental features of gene regulation2 and gather information on the mechanisms involved in establishing the gene expression patterns.
Recent advances in protein-protein interaction measurements, such as Alpha Screen Assay and Single Molecule coincidence analysis, coupled to cell-free expression, allow us to identify protein-protein interactions between transcription factors more systematically.
Key transcription factors (TFs) including SRY-related HMG box-containing protein 18 (SOX18), COUP-TFII, and prospero-related homeobox 1 (PROX1) are responsible for the molecular control of the lymphatic endothelial cell fate. Mutations or truncations present in the coding sequence of these TFs can cause a variety of human diseases. To understand the molecular pathologies, we want to study the changes in interactome and ask how many protein-protein interactions (PPI) are lost due to the change that the mutations may entail.