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Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2013 Mar 19; Vol. 110 (12), pp. 4691-6. Date of Electronic Publication: 2013 Mar 07. - Publication Year :
- 2013
-
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.
- Subjects :
- Animals
Asthma genetics
Asthma immunology
Asthma pathology
DNA Helicases genetics
Disease Models, Animal
GATA3 Transcription Factor genetics
Genetic Loci immunology
Inflammation genetics
Inflammation immunology
Inflammation pathology
Interferon-gamma genetics
Interferon-gamma immunology
Mice
Mice, Inbred BALB C
Multiprotein Complexes genetics
Nucleosomes genetics
Nucleosomes immunology
T-Box Domain Proteins genetics
T-Box Domain Proteins immunology
Th2 Cells pathology
Transcription, Genetic genetics
Cell Differentiation immunology
DNA Helicases metabolism
GATA3 Transcription Factor immunology
Multiprotein Complexes immunology
Th2 Cells immunology
Transcription, Genetic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 110
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 23471993
- Full Text :
- https://doi.org/10.1073/pnas.1220865110