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Rapid enhancer remodeling and transcription factor repurposing enable high magnitude gene induction upon acute activation of NK cells
Rapid enhancer remodeling and transcription factor repurposing enable high magnitude gene induction upon acute activation of NK cells
- Source :
- Immunity
- Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Immunity
- Accession number :
- edsair.doi.dedup.....7ad1806cd35645a8c74d4aa2f748034d