Grant: Discovery Grants Program - Individual

The development of the brain is regulated by expression of genes that are encoded by our DNA. The expression of these genes takes place in a regulated fashion, with only certain genes being expressed at specific times in specific cells. This tight regulation is mediated by epigenetic factors. Epigenetics refers to a set of factors that bind DNA to regulate gene expression without altering the DNA sequence. DNA is wrapped around proteins called histones to form units defined as nucleosomes. There are 4 categories of histones: H2A, H2B, H3 and H4. These histones are defined as "canonical", and they are fundamental regulators of gene expression. Canonical histones can be replaced by variants, similar proteins but with different properties that regulate gene expression in a unique way. Histone variants are incorporated or removed from the DNA by proteins called histone chaperones. By removing or incorporating variants in the DNA, histone chaperones are able to regulate gene expression and higher brain functions like memory formation. In this proposal we aim at investigating the role of specific chaperones of histone variant H2A.Z in the development of the brain. We hypothesize that, by regulating H2A.Z levels at specific genes, chaperones can regulate gene expression that is necessary to direct proper neurodevelopment. We will use cells as a model of neuronal development to characterize the position of H2A.Z on the DNA at different stages of development and to understand how H2A.Z can regulate gene expression. Then, we will use mouse embryos to impair the expression of H2A.Z chaperones and observe what are the consequences on the development of the nervous system. Overall, our research program will generate useful results to understand how our brain develops and what is the contribution of H2A.Z and its chaperones to this process.