Dataset Information


T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements.

ABSTRACT: 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.


PROVIDER: S-EPMC3535338 | BioStudies | 2012-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-11-16 | E-GEOD-31320 | ArrayExpress
1000-01-01 | S-EPMC4829694 | BioStudies
2013-01-01 | S-EPMC3606997 | BioStudies
2010-01-01 | S-EPMC2867662 | BioStudies
2010-01-01 | S-EPMC2943146 | BioStudies
2018-01-01 | S-EPMC6215836 | BioStudies
2013-01-01 | S-EPMC3832009 | BioStudies
2015-01-01 | S-EPMC4673438 | BioStudies
2010-01-01 | S-EPMC2807311 | BioStudies
2022-03-30 | GSE171408 | GEO