Abstract
GATA binding protein 3 (Gata3) is a GATA family transcription factor that controls differentiation of naïve CD4 T cells into T helper 2 (Th2) cells. However, it is unknown how Gata3 simultaneously activates Th2-specific genes while repressing those of other Th lineages. Here we show that chromodomain helicase DNA-binding protein 4 (Chd4) forms a complex with Gata3 in Th2 cells that both activates Th2 cytokine transcription and represses the Th1 cytokine IFN-γ. We define a Gata3/Chd4/p300 transcriptional activation complex at the Th2 cytokine loci and a Gata3/Chd4-nucleosome remodeling histone deacetylase repression complex at the Tbx21 locus in Th2 cells. We also demonstrate a physiological role for Chd4 in Th2-dependent inflammation in an in vivo model of asthmatic inflammation. Thus, Gata3/Chd4 forms functionally distinct complexes, which mediate both positive and negative gene regulation to facilitate Th2 cell differentiation.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Asthma / genetics
-
Asthma / immunology
-
Asthma / pathology
-
Cell Differentiation / immunology*
-
DNA Helicases / genetics
-
DNA Helicases / metabolism*
-
Disease Models, Animal
-
GATA3 Transcription Factor / genetics
-
GATA3 Transcription Factor / immunology*
-
Genetic Loci / immunology
-
Inflammation / genetics
-
Inflammation / immunology
-
Inflammation / pathology
-
Interferon-gamma / genetics
-
Interferon-gamma / immunology
-
Mice
-
Mice, Inbred BALB C
-
Multiprotein Complexes / genetics
-
Multiprotein Complexes / immunology*
-
Nucleosomes / genetics
-
Nucleosomes / immunology
-
T-Box Domain Proteins / genetics
-
T-Box Domain Proteins / immunology
-
Th2 Cells / immunology*
-
Th2 Cells / pathology
-
Transcription, Genetic / genetics
-
Transcription, Genetic / immunology*
Substances
-
GATA3 Transcription Factor
-
Gata3 protein, mouse
-
Multiprotein Complexes
-
Nucleosomes
-
T-Box Domain Proteins
-
T-box transcription factor TBX21
-
Interferon-gamma
-
Mi-2beta protein, mouse
-
DNA Helicases