Dynamic alterations in the conformation of the Ifng gene region during T helper cell differentiation.

Gene expression and silencing in eukaryotic systems can be controlled by regulatory elements acting over a distance. Here, we analyze chromatin conformation of the 24-kb region of the Ifng gene during CD4(+) T helper (Th) cell differentiation. We find that chromatin within this region is a highly flexible structure that undergoes dynamic changes during the course of transcriptional activation and silencing of the Ifng gene. Each Th subset displays a common core conformation in this gene region and unique features that distinguish neutral and effector Th1 and Th2 lineages. This chromatin configuration brings distal regions into close proximity to the gene. Th1 cells that produce high levels of IFN-gamma display the most open conformation. In contrast, IFN-gamma silent Th2 cells have a tightly closed conformation. Therefore, we postulate that there is a direct structure-function relationship between the spatial organization of the chromatin around the Ifng gene and its transcriptional potential.