EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming

ABSTRACT: Memory CD8+ T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, naïve 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.

INSTRUMENT(S): Thermo Scientific instrument model

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spleen

SUBMITTER: Abdulkader AZOUZ  

LAB HEAD: Stanislas GORIELY

PROVIDER: PXD014142 | Pride | 2019-06-06

REPOSITORIES: Pride