News Finding: They found that adding permeable alpha-ketoglutarate to the low interleukin 2 condition induced about a third of the gene program induced by high interleukin 2 relative to low interleukin 2 in T cells, while it inhibited about 10 percent of the genes that were more highly expressed in low interleukin 2 relative to high interleukin 2 conditions.
Paper Finding: In this study, we identified a connection between IL-2-and aKGsensitive metabolic states with CTCF binding dynamics, genome organization, and gene programming events in CD4 + Th1 cells.
News Context: These different concentrations of interleukin 2 signaling drive the cells to turn on different gene programs and develop gene programs similar to those from either effector or memory T cells. They found that adding permeable alpha-ketoglutarate to the low interleukin 2 condition induced about a third of the gene program induced by high interleukin 2 relative to low interleukin 2 in T cells, while it inhibited about 10 percent of the genes that were more highly expressed in low interleukin 2 relative to high interleukin 2 conditions. Alpha-ketoglutarate thus appears to be responsible for part, but not all, of interleukin 2's impact on T cell gene programming.
Paper Context: Collectively, the data are suggestive that aKG-sensitive metabolic events promote an initial mechanistic step, including enhancing CTCF binding at select sites, which is subsequently translated into consequences on gene expression in a contextdependent manner. In this study, we identified a connection between IL-2-and aKGsensitive metabolic states with CTCF binding dynamics, genome organization, and gene programming events in CD4 + Th1 cells. The data suggested that aKG-sensitive metabolic events are integrated by selective changes in CTCF genomic distribution, but this is interpreted in a context-dependent manner, which in part is influenced by the enhancer landscape in the cell.