Overlying gene regulatory mechanisms is the local chromatin architecture that controls the accessibility of genes to specific transcription factors and the ability of transcription factors to interact over long distances. Our lab investigates the role of chromatin and epigenetic mechanisms in the regulation of gene expression and the control of cellular programming in the immune system. In our model systems, we seek to elucidate the molecular processes that control 1) major histocompatibility complex class II (MHC-II) genes, 2) programmed death-1 (PD-1); and 3) differentiation processes in both T cells and B cells. In addition to evaluating human cell lines and samples, we employ animal, cellular, and molecular genetic approaches in our studies. Mice containing deleted regulatory elements are being created to develop in vivo model systems to interrogate gene assembly and chromatin modification questions. Additionally, mice with conditional targeted mutations in genes critical to chromatin and epigenetic functions are used to dissect their role in immune cell differentiation. Using these mice global, genome-wide patterns of histone modifications, DNA methylation, and transcription factor binding sites are examined. Through these studies we hope to develop higher order models of gene regulation and the development of effective immune system responses. Our studies will define the roles of specific factors and pathways that may be targeted for immune based therapies in the treatment of infectious disease, cancer, autoimmunity, and vaccination.