H3K27 Methylation Dynamics during CD4 T Cell Activation: Regulation of JAK/STAT and IL12RB2 Expression by JMJD3

Abstract

The changes to the epigenetic landscape in response to antigen during CD4 T cell activation have not been well characterized. While CD4 T cell subsets have been mapped globally for numerous epigenetic marks, little has been done to study their dynamics early after activation. We have studied changes to promoter H3K27me3 during activation of human naïve and memory CD4 T cells. Our results show that these changes occur relatively early (1 day) after activation of both naïve and memory cells, and that demethylation is the predominant change to H3K27me3 at this time point, reinforcing high expression of target genes. Additionally, inhibition of the H3K27 demethylase, JMJD3, in naïve CD4 T cells demonstrates how critically important molecules required for T cell differentiation, such as JAK2 and IL12RB2, are regulated by H3K27me3. Our results demonstrate that H3K27me3 is a dynamic and important epigenetic modification during CD4 T cell activation, and that JMJD3-driven H3K27 demethylation is critical for CD4 T cell function.

Circulating growth/differentiation factor 15 is associated with human CD56bright natural killer cell dysfunction and nosocomial infection in severe systemic inflammation

“…The binding affinity of some of these transcriptions factors depends on genetic variants and influences the transcriptional activity of the IL-12RB2 gene [53]. Moreover, epigenetic modifications of the IL-12RB2 locus have been reported [54]. Any of these regulatory mechanisms should be considered in future studies on the mechanisms that cause the modulation of CD56 bright NK cells in systemic inflammation.…”

Mapping Influenza-Induced Posttranslational Modifications on Histones from CD8+ T Cells

“…However, trimethylation at lysine 9 was present in 12 out of the 23 isoforms we confidently identified. Both H3K4me3 and H3K27me3 play an essential role in polarization and activation of immune cells, including CD8+ T cells [16,17,[73][74][75][76]. Interestingly, we identified several species with lysine 9 (H3K9) methylations and H3K27 di-and trimethylations that were exclusively identified in BAL, expecially when PTMs were absent in the intervening region [ Fig 3D].…”

Vitamin C and immune cell function in inflammation and cancer

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“…Profound demethylation of histone H3K27 is observed after activation in CD4 + T cells and corresponds to pathways crucial to T-cell function, including T-cell activation and the regulation of the JAK/STAT pathways [ 151 , 152 ]. Deletion of the histone demethylase JMJD3 was found to regulate gene expression resulting in T H 2 and T H 17 differentiation and inhibiting T H 1 and Treg cell differentiation via altered methylation status of H3K27 and/or H3K4 [ 153 , 154 ].…”