The Tyler Laboratory studies the epigenetic regulation of gene expression and genomic integrity. All the activities of the Eukaryotic genome, including DNA repair, gene expression, and DNA replication are tightly regulated by packaging the DNA together with histones into chromatin and by dynamic alterations to this chromatin structure.
The goal of our research is to discover novel ways in which the chromatin structure is altered during gene expression and double-strand DNA repair, and to understand how these chromatin dynamics regulate these key nuclear processes. For example, we recently showed for the first time that histones are acetylated and then deacetylated during the process of double-strand DNA repair via homologous recombination, and that failure to do so results in cell death. We have also recently discovered that the removal of histones from promoter regions is essential for transcriptional activation, while the replacement of histones onto promoter regions is essential for transcriptional repression.
Our lab is now defining how these and other chromatin changes occur and the molecular mechanisms by which they regulate normal gene expression patterns and double-strand DNA repair. Our studies use a combination of molecular genetic in budding yeast, tissue culture studies, biochemistry, biophysics and structural approaches. The proteins and processes that we study are so highly conserved through eukaryotic evolution, that what we learn in the highly genetically malleable yeast system is directly relevant to the situation in humans. In addition to learning how chromatin regulates fundamental processes in the cell, our studies are helping us to understand how defects in the chromatin structure lead to gene dysfunction and genomic instability, in turn causing human aging and disease states including cancer and leukemia.