Regulation of gene expression is an essential process for the development and maintenance of living organisms. The first step in decoding the information contained in DNA is called transcription. This process involves many proteins, notably nuclear receptors, which have the ability to bind to DNA and will allow precise control of gene expression. The activation of these receptors often requires binding of small molecules, such as hormones, which will then cause a change in receptor conformation. This conformational change promotes the dissociation of proteins that have a negative effect on the activity of nuclear receptors (corepressors), which then allows the recruitment of proteins with positive effects (coactivators). This will then facilitate the accessibility of the general transcriptional machinery on specific DNA regions, leading to gene expression.
The proposed research program aims to understand the role of the chromatin environment and structure of DNA in the regulation of gene expression controlled by nuclear receptors, in pathological context (breast and prostate cancer). To accomplish our goals, we will exploit a variety of cutting edge molecular biology and bioinformatics tools permitting a detailed investigation of gene regulation. Given the importance of nuclear receptors in human physiology, their role in diseases pathogenesis and their importance as therapeutic targets, a comprehensive understanding of their function should have an impact on the development of new drugs for the treatment of pathologies such as breast and prostate cancer.