| Autor: |
Enric Mocholi, Laura Russo, Keshav Gopal, Andrew Ramstead, Sophia M. Hochrein, HarmJan Vos, Geert Geeven, Adeolu Adegoke, Anna Hoekstra, Robert van Es, José Ramos Pittol, Sebastiaan Vastert, Jared Rutter, Timothy Radstake, Jorg van Loosdregt, Celia Berkers, Michal Mokry, Colin Anderson, Ryan O'Connell, Martin Vaeth, John Ussher, Boudewijn Burgering, Paul Coffer |
| Rok vydání: |
2022 |
| Popis: |
Upon antigen-specific T Cell Receptor (TCR) engagement, human CD4+ T cells proliferate and differentiate, a process associated with rapid transcriptional changes and metabolic reprogramming. Here, we show that generation of extra-mitochondrial pyruvate is an essential step for acetyl-CoA production and subsequent H3K27ac-mediated epigenome remodeling. In contrast, neither acetate/ACSS2 nor citrate/ACLY metabolism are required for activation-induced transcriptional changes. Furthermore, T cell activation results in the nuclear translocation of PDC and its association with both the p300 acetyltransferase and histone H3K27ac. These data support tight integration of metabolic and histone-modifying enzymes, allowing metabolic reprogramming to fuel CD4+ T cell activation. Targeting this pathway may provide a novel therapeutic approach to specifically regulate antigen-driven T cell activation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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