T-bet and GATA3 regulate the CD4+ T cell Th1/Th2 cell fate decision but little 
is known about the interplay between these factors outside of the murine Ifng 
and Il4/Il5/Il13 loci. Here we show that T-bet and GATA3 bind to multiple distal 
sites at immune regulatory genes in human effector T cells. These sites display 
markers of functional elements, act as enhancers in reporter assays and are 
associated with a requirement for T-bet and GATA3. Furthermore, we demonstrate 
that both factors bind distal sites at Tbx21 and that T-bet directly activates 
its own expression. We also show that in Th1 cells, GATA3 is distributed away 
from Th2 genes, instead occupying T-bet binding sites at Th1 genes, and that 
T-bet is sufficient to induce GATA3 binding at these sites. We propose these 
aspects of T-bet and GATA3 function are important for Th1/Th2 differentiation 
and for understanding transcription factor interactions in other T cell lineage 
decisions.