Hierarchical regulation of the resting and activated T cell epigenome by major transcription factor families

Zhong et al. utilize B6/Cast F1 hybrid mice to examine transcriptional regulation of T cell gene expression upon activation induced by viral challenge. They describe gene accessibility changes that lead to differential gene expression and report a hierarchy of transcription factor families that mediate the chromatin dynamics. T cell activation, a key early event in the adaptive immune response, is subject to elaborate transcriptional control. In the present study, we examined how the activities of eight major transcription factor (TF) families are integrated to shape the epigenome of naive and activated CD4 and CD8 T cells. By leveraging extensive polymorphisms in evolutionarily divergent mice, we identified the 'heavy lifters' positively influencing chromatin accessibility. Members of Ets, Runx and TCF/Lef TF families occupied the vast majority of accessible chromatin regions, acting as 'housekeepers', 'universal amplifiers' and 'placeholders', respectively, at sites that maintained or gained accessibility upon T cell activation. In addition, a small subset of strongly induced immune response genes displayed a noncanonical TF recruitment pattern. Our study provides a key resource and foundation for the understanding of transcriptional and epigenetic regulation in T cells and offers a new perspective on the hierarchical interactions between critical TFs.

Automated summary

Zhong et al. studied the transcriptional regulation of T cell gene expression upon viral challenge using B6/Cast F1 hybrid mice. They found that members of Ets, Runx, and TCF/Lef transcription factor families play key roles in maintaining or increasing chromatin accessibility during T cell activation. Some highly induced immune response genes exhibit a noncanonical TF recruitment pattern.