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

• Published in: Nature immunology Vol. 23; no. 1; pp. 122 - 134
• Main Authors: Zhong, Yi, Walker, Sarah K., Pritykin, Yuri, Leslie, Christina S., Rudensky, Alexander Y., van der Veeken, Joris
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2022; Nature Publishing Group
• Subjects: 631/250/2502/2170; 631/250/2502/248; Adaptive immunity; Adaptive Immunity - immunology; Animals; Biomedical and Life Sciences; Biomedicine; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell activation; Chromatin; Chromatin - immunology; Divergence; Epigenesis, Genetic - immunology; Epigenetics; Epigenome - immunology; ETS protein; Gene expression; Gene Expression Regulation - immunology; Gene regulation; Immune response; Immunology; Infectious Diseases; LEF protein; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Male; Mice; Resource; Transcription factors; Transcription Factors - immunology
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/s41590-021-01086-x

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. 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.