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Zhang, Jiang; Le Gras, Stéphanie; Pouxvielh, Kevin; Faure, Fabrice; Fallone, Lucie; Kern, Nicolas; Moreews, Marion; Mathieu, Anne-Laure; Schneider, Raphaël; Marliac, Quentin; Jung, Mathieu; Berton, Aurore; Hayek, Simon; Vidalain, Pierre-Olivier; Marçais, Antoine; Dodard, Garvin; Dejean, Anne; Brossay, Laurent; Ghavi-Helm, Yad; Walzer, Thierry
Nature communications, 09/2021, Letnik: 12, Številka: 1Journal Article
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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