Chromatin remodeling and T helper subset differentiation

The T helper subsets Th1 and Th2 regulate specific types of immune response s by producing distinct sets of cytokines. Differentiation of the T helper subsets from their common precursors, naive CD4+ T cells, is induced by ant igen stimulation and controlled by various other conditions. Of these condi tions, the contributions of the cytokine environment have been the best cha racterized. The presence of interleukin-4 (IL-4) directs the differentiatio n ton ards Th2 cells, whereas IL-12 induces Th1 differentiation. The Th2 si gnature cytokine genes encoding IL-4, IL-13, and IL-5 are clustered, and no ncoding regions such as the intergenic region of the IL-4 and IL-13 genes a re highly conserved from mice to humans, Alteration of the chromatin struct ure of this Th2 cytokine cluster region is detected as nuclease-accessible regions specific to Th2 cells, Activation of STAT6 promotes Th2 differentia tion by inducing Th2-specific transcription factors, including GATA3, Expre ssion of GATA3 induces Th2 differentiation and enhances the Th2 cell-specif ic chromatin accessibility, indicating that GATA3 is a key protein that reg ulates differentiation through chromatin remodeling, T helper subset differ entiation provides a good system to study gene expression regulation at the chromatin level.