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Published on: December 17, 2015
H3K27 Methylation Dynamics during CD4 T Cell Activation: Regulation of JAK/STAT and IL12RB2 Expression by JMJD3
Sarah A LaMere1, Ryan C Thompson2, Xiangzhi Meng2
1Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037 salamere@ucsd.edu.
Abstract:
The changes to the epigenetic landscape in response to Ag during CD4 T cell activation have not been well characterized. Although 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 naive and memory CD4 T cells. Our results show that these changes occur relatively early (1 d) after activation of naive 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 naive CD4 T cells demonstrates how critically important molecules required for T cell differentiation, such as JAK2 and IL12RB2, are regulated by H3K27me3. Our results show 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.
Insights
Epigenetic changes, specifically H3K27 trimethylation (H3K27me3) demethylation, occur early during CD4 T cell activation. This dynamic epigenetic modification, driven by JMJD3, is crucial for T cell function and gene expression.
Area of Science:
- Immunology
- Epigenetics
- Molecular Biology
Background:
- The dynamic epigenetic landscape of CD4 T cell activation is not fully understood.
- Early changes in epigenetic marks during T cell activation require further investigation.
Purpose of the Study:
- To characterize the dynamic changes in promoter H3K27me3 during human naive and memory CD4 T cell activation.
- To investigate the role of the H3K27 demethylase JMJD3 in regulating CD4 T cell differentiation and function.
Main Methods:
- Analysis of promoter H3K27me3 modifications in naive and memory CD4 T cells post-activation.
- Inhibition of JMJD3 in naive CD4 T cells to assess its impact on gene expression and T cell differentiation.
Main Results:
- Demethylation of H3K27me3 occurs early (1 day) after CD4 T cell activation in both naive and memory cells.
- H3K27me3 demethylation correlates with increased expression of target genes.
- JMJD3 inhibition in naive CD4 T cells impairs the expression of critical differentiation molecules like JAK2 and IL12RB2.
Conclusions:
- H3K27me3 is a dynamic epigenetic mark critical for CD4 T cell activation.
- JMJD3-mediated H3K27me3 demethylation is essential for regulating gene expression and ensuring proper CD4 T cell function and differentiation.
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