GSE159505
Trithorax Cxxc1-directed epigenetic dynamics licensing CD4+ T cell differentiation
Different dynamics of gene expression are observed during cell differentiation. In T-cells, genes that are turned on early, or turned off and stay off have been thoroughly studied. However, genes that are initially turned off but then turned on again after stimulation has ceased have not been defined; they are obviously important, especially in the context of acute versus chronic inflammation. Using the Th1/Th2 differentiation paradigm, we found that Cxxc1 subunit of the Trithorax complex directs transcription of genes initially downregulated by TCR stimulation but upregulated again in a later phase. The late upregulation of these genes was impaired either by prolonged TCR stimulation or Cxxc1-deficiency, which led to decreased expression of Trib3 and Klf2 in Th1 and Th2 cells, respectively. Loss of Cxxc1 resulted in enhanced pathogenicity in allergic airway inflammation in vivo. Thus, Cxxc1 plays essential roles in the establishment of a proper CD4+ T-cell immune system via epigenetic control of a specific set of genes. Overall design: Different dynamics of gene expression during T cell differentiation assessed by ATAC-seq, ChIP-seq and RNA-seq.