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The polycomb protein Ezh2 regulates differentiation and plasticity of CD4(+) T helper type 1 and type 2 cells
- Source :
- Immunity. 39(5)
- Publication Year :
- 2013
-
Abstract
- After antigen encounter by CD4 + Tcells, polarizing cytokines induce the expression of master regulators that control differentiation. Inactivation of the histone methyltransferase Ezh2 was found to specifically enhance T helper 1 (Th1) and Th2 cell differentiation and plasticity. Ezh2 directly bound and facilitated correct expression of Tbx21 and Gata3 in differentiating Th1 and Th2 cells, accompanied by substantial trimethylation at lysine 27 of histone 3 (H3K27me3). In addition, Ezh2 deficiency resulted in spontaneous generation of discrete IFN-γ and Th2 cytokine-producing populations in nonpolarizing cultures, and under these conditions IFN-γ expression was largely dependent on enhanced expression of the transcription factor Eomesodermin. Invivo, loss of Ezh2 caused increased pathology in a model of allergic asthma and resulted in progressive accumulation of memory phenotype Th2 cells. This study establishes a functional link between Ezh2 and transcriptional regulation of lineage-specifying genes in terminally differentiated CD4 + Tcells. Refereed/Peer-reviewed
- Subjects :
- Male
Cellular differentiation
Immunology
Eomesodermin
macromolecular substances
GATA3 Transcription Factor
Methylation
Histones
Mice
Th2 Cells
Th1 cells
T-Lymphocyte Subsets
Transcriptional regulation
Immunology and Allergy
Animals
Enhancer of Zeste Homolog 2 Protein
Cells, Cultured
Sequence Deletion
Regulation of gene expression
Lymphokines
biology
EZH2
GATA3
Polycomb Repressive Complex 2
Cell Differentiation
Histone-Lysine N-Methyltransferase
asthma
Th1 Cells
Asthma
Cell biology
Mice, Inbred C57BL
Histone
Infectious Diseases
Gene Expression Regulation
Histone methyltransferase
biology.protein
Cancer research
Histone Methyltransferases
Female
T-Box Domain Proteins
Immunologic Memory
Protein Processing, Post-Translational
Interferon-gamma Release Tests
Subjects
Details
- ISSN :
- 10974180
- Volume :
- 39
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Immunity
- Accession number :
- edsair.doi.dedup.....ccd9debcb4bcfb47ef1fedb6a727a25b