Differentiation of naive CD4 T cells into 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 chromatin immunoprecipitation assay 
coupled with massive parallel sequencing analysis revealed that GATA3 bound to 
1279 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 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, whereas 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.