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

Autor: Zhong Y; Howard Hughes Medical Institute and Immunology Program, Sloan Kettering Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Shanghai Immune Therapy Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Walker SK; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.; Quantitative and Computational Biology Graduate Program, Princeton University, Princeton, NJ, USA., Pritykin Y; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.; Department of Computer Science, Princeton University, Princeton, NJ, USA., Leslie CS; Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Rudensky AY; Howard Hughes Medical Institute and Immunology Program, Sloan Kettering Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY, USA. rudenska@mskcc.org., van der Veeken J; Howard Hughes Medical Institute and Immunology Program, Sloan Kettering Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY, USA. joris.van.der.veeken@imp.ac.at.; Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria. joris.van.der.veeken@imp.ac.at.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2022 Jan; Vol. 23 (1), pp. 122-134. Date of Electronic Publication: 2021 Dec 22.
DOI: 10.1038/s41590-021-01086-x
Abstrakt: 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.
(© 2021. Springer Nature America, Inc.)
Databáze: MEDLINE
Externí odkaz: