Transcription Regulation Staff

The Lymphoid Signal Transduction Biology Lab studies the mechanisms of the regulatory targeting of p300 co-activator complexes in activated T-cells. Much of the work has recently focussed on defining the functional partitioning of p300 within the molecular anatomy of the activated T-cells nucleus. This work has pursued two major lines of investigation. In the first we are utilizing chromatin precipitation assays to determine the occupancy times of p300 at the specific promoter regions within the human genome under selective conditions of T-cell activation and immuno-suppression. To further this goal, we are developing a promoter array methodology that will allow a kinetic assessment of the occupancy of p300 and other proteins at genomic sequences during T-cell activation. In the second, we are beginning to define the covalent modifications and the protein-protein binding partners of p300 in activated T-cells. To facilitate this, we are combining "nearest neighbor" detection techniques with proteomic analysis strategies to detail the dynamic changes in the association of p300 with different nuclear factors and compartments during T-cell activation. We are currently adapting both in situ and in vivo cross-linking strategies toward that end. The goal is to assemble the data from this combined genomic and proteomic approach to define the rules of interaction of p300 within the dynamically changing microenvironment of the activated T-cell nucleus.