GSE28292
Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3
Differentiation of naive CD4 T cells into type 2 helper (Th2) cells is accompanied by chromatin remodeling and increased expression of a set of Th2-specific genes including those encoding Th2 cytokines.  IL-4-mediated STAT6 activation induces high levels of transcription of GATA3, a master regulator of Th2 cell differentiation, and enforced expression of GATA3 induces Th2 cytokine expression.  However, it remains unclear whether the expression of other Th2-specific genes is induced directly by GATA3.  A genome-wide unbiased ChIP-seq analysis revealed that GATA3 bound to 1,279 genes selectively in Th2 cells, and 101 genes in both Th1 and Th2 cells.  Simultaneously, we identified 26 highly Th2-specific STAT6-dependent inducible genes by a DNA microarray analysis-based three-step selection processes, and among them 17 genes showed GATA3 binding.  We assessed dependency on GATA3 for the transcription of these 26 Th2-specific genes, and 10 genes showed increased transcription in a GATA3-dependent manner while 16 genes showed no significant responses.  The transcription of the 16 GATA3-nonresponding genes was clearly increased by the introduction of an active form of STAT6, STAT6VT.  Therefore, although GATA3 has been recognized as a master regulator of Th2 cell differentiation, many Th2-specific genes are not regulated by GATA3 itself but in collaboration with STAT6. Overall design: Th1 and Th2  subsets are profiled for mRNA expression Examination of GATA3-binding and 3 different histone modifications in Th1 and Th2 cells.