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Nat Commun. 2019 Jul 24;10(1):3306. doi: 10.1038/s41467-019-11233-6.

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

Author information

1
Université Libre de Bruxelles, Institute for Medical Immunology (IMI), Gosselies, 6041, Belgium.
2
Université Catholique de Louvain, Institut de Duve, Brussels, 1200, Belgium.
3
Université Libre de Bruxelles, Laboratory of Cancer Epigenetics, Brussels, 1070, Belgium.
4
Université Libre de Bruxelles, Interuniversity Institute of Bioinformatics in Brussels (IB2), Brussels, 1050, Belgium.
5
Université Libre de Bruxelles, Institute for Medical Immunology (IMI), Gosselies, 6041, Belgium. stgoriel@ulb.ac.be.

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.

PMID:
31341159
PMCID:
PMC6656725
DOI:
10.1038/s41467-019-11233-6
[Indexed for MEDLINE]
Free PMC Article

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