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

Research paper by Jiang J Zhang, Stéphanie S Le Gras, Kevin K Pouxvielh, Fabrice F Faure, Lucie L Fallone, Nicolas N Kern, Marion M Moreews, Anne-Laure AL Mathieu, Raphaël R Schneider, Quentin Q Marliac, Mathieu M Jung, Aurore A Berton, Simon S Hayek, Pierre-Olivier PO Vidalain, Antoine A Marçais, et al.

Indexed on: 16 Sep '21Published on: 16 Sep '21Published in: Nature communications



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. © 2021. The Author(s).