E-GEOD-51079 - The polycomb protein Ezh2 regulates differentiation and plasticity of CD4 T helper type-1 and type-2 cells [ChIP-seq]
Released on 24 September 2013, last updated on 25 November 2013
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.
Akane Suzuki, Atsushi Onodera, Chiaki Iwamura, Damon Tumes, Hiroyuki Hosokawa, Kenta Shinoda, Koji Tokoyoda, Shinichiro Motohashi, Toshinori Nakayama, Yusuke Endo, Yutaka Suzuki