Rapid enhancer remodeling and transcription factor repurposing enable high magnitude gene induction upon acute activation of NK cells
| Autor: | Hong-Wei Sun, Chen Yao, Fred P. Davis, Kiyoshi Hirahara, Tasha A. Morrison, Vittorio Sartorelli, Yuka Kanno, Beatrice Zitti, Yohei Mikami, Giuseppe Sciumè, Sadie Signorella, Stephen R. Brooks, Difeng Fang, Han-Yu Shih, Dragana Jankovic, Hiroyuki Nagashima, Alejandro V. Villarino, Shingo Nakayamada, John J. O'Shea |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunology Gene Expression Biology Article 03 medical and health sciences Mice 0302 clinical medicine Immunology and Allergy Animals Enhancer Transcription factor Epigenomics Regulation of gene expression Innate immune system Gene Expression Profiling Macrophages Innate lymphoid cell Chromatin Immunity Innate Cell biology Killer Cells Natural Mice Inbred C57BL 030104 developmental biology Infectious Diseases Enhancer Elements Genetic de novo enhancers innate lymphoid cells lineage defining transcription factors natural killer cells poised enhancers signal regulated transcription factors signal transducer and activator of transcription (STAT) protein super-enhancers T-bet toxoplasma Gondii infection Gene Expression Regulation Regulatory sequence 030220 oncology & carcinogenesis Female Toxoplasma Toxoplasmosis Transcription Factors |
| Zdroj: | Immunity |
| Popis: | Summary Innate immune responses rely on rapid and precise gene regulation mediated by accessibility of regulatory regions to transcription factors (TFs). In natural killer (NK) cells and other innate lymphoid cells, competent enhancers are primed during lineage acquisition, and formation of de novo enhancers characterizes the acquisition of innate memory in activated NK cells and macrophages. Here, we investigated how primed and de novo enhancers coordinate to facilitate high-magnitude gene induction during acute activation. Epigenomic and transcriptomic analyses of regions near highly induced genes (HIGs) in NK cells both in vitro and in a model of Toxoplasma gondii infection revealed de novo chromatin accessibility and enhancer remodeling controlled by signal-regulated TFs STATs. Acute NK cell activation redeployed the lineage-determining TF T-bet to de novo enhancers, independent of DNA-sequence-specific motif recognition. Thus, acute stimulation reshapes enhancer function through the combinatorial usage and repurposing of both lineage-determining and signal-regulated TFs to ensure an effective response. |
| Databáze: | OpenAIRE |
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