UNDERSTANDING THE ROLE OF THE NUCLEOSOME REMODELING AND DEACETYLASE COMPLEX IN GLUCOCORTICOID GENE EXPRESSION

Abstract

Creating therapies that minimize off target effects is essential for disease treatment but a comprehensive understanding of the underlying mechanisms are crucial. Lysine deacetylase inhibitors are approved for clinical use in treatment of several diseases but the full effects are not understood. Specific lysine deacetylase inhibitors have been found to have a significant effect on metabolism leading to the discovery of the interplay between glucocorticoid receptor activated genes and lysine deacetylase enzymes. These enzymes are present in multi-protein complexes of which the functions are poorly understood. Furthermore functions of the individual subunits of each of these complexes need to be explored. The Smith lab aims to determine the mechanisms through which lysine deacetylases activate glucocorticoid gene transcription. This project is specifically seeking to identify the role of the lysine deacetylase 1/2 containing nucleosome remodeling complex.