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

Archive ouverte

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

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion