Sequential actions of EOMES and T-BET promote stepwise maturation of natural killer cells - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2021

Sequential actions of EOMES and T-BET promote stepwise maturation of natural killer cells

Abstract

EOMES and T-BET are related T-box transcription factors that control natural killer (NK) cell development. Here we demonstrate that EOMES and T-BET regulate largely distinct gene sets during this process. EOMES is dominantly expressed in immature NK cells and drives early lineage specification by inducing hallmark receptors and functions. By contrast, T-BET is dominant in mature NK cells, where it induces responsiveness to IL-12 and represses the cell cycle, likely through transcriptional repressors. Regardless, many genes with distinct functions are co-regulated by the two transcription factors. By generating two gene-modified mice facilitating chromatin immunoprecipitation of endogenous EOMES and T-BET, we show a strong overlap in their DNA binding targets, as well as extensive epigenetic changes during NK cell differentiation. Our data thus suggest that EOMES and T-BET may distinctly govern, via differential expression and co-factors recruitment, NK cell maturation by inserting partially overlapping epigenetic regulations.
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Dates and versions

hal-03357265 , version 1 (28-09-2021)

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Jiang Zhang, Stéphanie Le Gras, Kevin Pouxvielh, Fabrice Faure, Lucie Fallone, et al.. Sequential actions of EOMES and T-BET promote stepwise maturation of natural killer cells. Nature Communications, 2021, 12 (1), pp.5446. ⟨10.1038/s41467-021-25758-2⟩. ⟨hal-03357265⟩
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