Functionally polarized CD4 T helper (Th) cells, such as Th1, Th2, and Th17 cells, are essential for the regulation of acquired immunity. Differentiation of naïve CD4 T cells into Th2 cells is characterized by chromatin remodeling and the induced expression of a set of Th2-specific genes, which include Th2 cytokine genes. In the first stage of this differentiation, a Th2-skewing cytokine environment, especially IL-4, induces STAT6 activation. Activated STAT6 increases the expression of GATA3, a master regulator of Th2 cell differentiation, via direct binding to the Gata3 gene locus. This transcriptional induction of Gata3 mRNA during Th2 cell differentiation is accompanied by dynamic changes in the binding patterns of two epigenetic modification proteins such as Polycomb and Trithorax complexes. Consequently, expressed GATA3 epigenetically modifies and upregulates Th2-specific genes to establish Th2 cell identity. This identity is maintained by high-level expression of the Gata3 gene controlled by Menin, which is a member of the Trithorax proteins, after cycles of cultivation in vitro and a long-term resting state in vivo. Thus, the Menin-GATA3 axis handles the Th2-specific gene regulatory network.
Part of the book: Gene Expression and Regulation in Mammalian Cells