The polycomb protein Ezh2 regulates differentiation and plasticity of CD4 T helper type-1 and type-2 cells [ChIP-seq]
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ABSTRACT: Following antigen encounter by CD4 T cells, polarizing cytokines induce the expression of master regulators that control differentiation. Inactivation of the histone methyltransferase Ezh2 was found to specifically enhance T-helper (Th)1 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 tri-methylation at lysine 27 of histone 3 (H3K27-Me3). In addition, Ezh2 deficiency resulted in spontaneous generation of discrete IFN-γ and Th2 cytokine-producing populations in non-polarizing cultures, and under these conditions IFN-γ expression was largely dependent on enhanced expression of the transcription factor Eomesodermin. In vivo, 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 T cells. Examination of Ezh2 binding in Th1 and Th2 cells.
ORGANISM(S): Mus musculus
SUBMITTER: Atsushi Onodera
PROVIDER: E-GEOD-51079 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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