Exploring the landscape and function of chromatin atomic-scale dynamics
The Sanulli lab investigates the biophysical principles of the genome to better understand how the access to genetic information is dynamically regulated in space and time to achieve specialized cellular functions. In cells, eukaryotic DNA is associated with proteins to form a complex matrix called chromatin. Nucleosomes, the most fundamental unit of chromatin, are are like spools of proteins around which the DNA is tightly wrapped. Nucleosomes form long chains like beads on a string that are further folded in three-dimensional assemblies. The architecture of these assemblies regulates access to genes, and it is therefore crucial for determining cell identity and for proper cellular functions. Recent findings have challenged classical models of chromatin organization at different levels. First, we appreciated that chains of nucleosomes are folded in structures that are less ordered and less discrete than previously thought. Second, we realized that nucleosomes have a malleable core that can undergo dynamic structural changes and regulate chromatin 3D folding. Building on our recent discoveries, we are interested in dissecting the dynamic structural changes at the atomic scale within nucleosomes and nucleosome chains, and how such dynamics regulate gene expression. We hypothesize that the nucleosome core represents a hub for chromatin regulation and that the changes in its structure might represent an essential mechanism to regulate genome three-dimensional organization and gene expression. By applying a combination of biophysical methods, we will measure the extent of chromatin dynamics at the atomic scale. By leveraging cell biology and genetics, we will probe how such dynamics regulate cell identity. Our work will advance our fundamental understanding of genome regulation and provide insights into the mechanisms underlying cell fate decisions in development.