Grant: Operating Grant

All cells in a multicellular organism contain the same genetic material. Despite this fact, different cell types must carry out different functions. How each cell expresses the required proteins at the correct times and represses unnecessary ones is a primary goal of gene regulation. Deregulation of this process can result in malfunctioning cells, cell death or uncontrolled growth (cancer). It is becoming increasingly clear that the remodeling of chromosome structure is an intricate part of the process controlling gene expression. Activities involved in this remodeling include multiprotein complexes which disrupt the basic structure of the chromosomes, the nucleosome, where DNA is wrapped around a structural protein core. These complexes are highly conserved in eukaryotes throughout evolution from unicellular organisms (ex. yeast) to mammals. They are intimately linked to gene transcription control and implicated in the development of many human cancers. Subunits of these activities interact with viral oncogene and tumor suppressor gene products. Our goal is to characterize the structure and functional roles of NuA4, a specific multisubunit histone acetyltransferase complex essential for cell viability. A combination of molecular biology, genetics, biochemistry and functional genomic techniques will be used to elucidate how this activity controls cell proliferation and gene expression, and also to characterize its role in the maintenance of the genome. Studying the fundamental processes which govern cell growth and differentiation allows us to better understand the mechanisms of a properly functioning cell. This in turn will point us to new scientific approaches in applied research and ultimately lay the grounds for developing new industrial production systems, diagnostic tools and therapies.