Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25758-2
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Funding
- Agence Nationale de la Recherche (ANR)
- Institut National du Cancer
- Institut National de la Sante et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS)
- Universite Claude Bernard Lyon1
- ENS de Lyon
- China Scholarship Council (CSC)
- FRM grant [AJE20161236686]
- NIH [AI46709, AI122217]
- [3R01AI122217-S1]
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EOMES and T-BET, two related transcription factors, regulate distinct developmental processes in Natural Killer cell development by sharing a large proportion of target genes but exhibiting differential expression patterns and associated co-factors.
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. Natural Killer cell development is controlled by two related transcription factors, Eomes and T-bet. Authors show here that while the two factors share a large proportion of their target genes, they regulate distinct developmental processes by differing in their pattern of expression and in their associated co-factors.
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