Journal Article

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

Mathieu, Anne-Laure, Infection virale, métabolisme et immunité - Viral Infection, Metabolism and Immunity [CIRI] (CIRI-VIRIMI) ; Centre International de Recherche en Infectiologie (CIRI) ; École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) ; Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National

2021

Overview

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.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK,Nature Portfolio
• Subject: 13/1 / 13/21 / 13/31 / 13/95 / 14 / 14/19 / 38 / 38/91 / 45 / 45/15 / 631/136/232/2058 / 631/250/1620/1342 / 631/250/2502/2170 / 631/250/2504/2506 / Animals / Base Sequence / Bone Marrow Cells - cytology / Bone Marrow Cells - immunology / CD11b Antigen - genetics / CD11b Antigen - immunology / Cell cycle / Cell Cycle - drug effects / Cell Cycle - genetics / Cell Cycle - immunology / Cell Differentiation / Cell Lineage - drug effects / Cell Lineage - genetics / Cell Lineage - immunology / Chromatin / Deoxyribonucleic acid / Differentiation (biology) / DNA / Epigenesis, Genetic - immunology / Epigenetics / Genes / Humanities and Social Sciences / Immunology / Immunoprecipitation / Interleukin 12 / Interleukin-12 - pharmacology / Killer Cells, Natural - cytology / Killer Cells, Natural - drug effects / Killer Cells, Natural - immunology / Life Sciences / Male / Maturation / Mice / Mice, Inbred C57BL / Mice, Transgenic / multidisciplinary / Natural killer cells / Promoter Regions, Genetic / Protein Binding / Repressors / Science / Science (multidisciplinary) / Spleen - cytology / Spleen - immunology / T-Box Domain Proteins - deficiency / T-Box Domain Proteins - genetics / T-Box Domain Proteins - immunology / Transcription factors / Transcription, Genetic / Tumor Necrosis Factor Receptor Superfamily, Member 7 - genetics / Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology