First Author | Istaces N | Year | 2019 |
Journal | Nat Commun | Volume | 10 |
Issue | 1 | Pages | 3306 |
PubMed ID | 31341159 | Mgi Jnum | J:281085 |
Mgi Id | MGI:6362084 | Doi | 10.1038/s41467-019-11233-6 |
Citation | Istaces N, et al. (2019) EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming. Nat Commun 10(1):3306 |
abstractText | Memory CD8(+) T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, naive CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these innate memory CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming is secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, EOMES is found within chromatin-associated complexes containing BRG1 and promotes the recruitment of this chromatin remodelling factor. Also, the in vivo acquisition of EOMES-dependent program is BRG1-dependent. In conclusion, our results support a strong epigenetic basis for the EOMES-driven establishment of CD8(+) T cell innate memory program. |