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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

Authors :
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
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.

Details

Language :
English
Database :
OpenAIRE
Journal :
Immunity
Accession number :
edsair.doi.dedup.....7ad1806cd35645a8c74d4aa2f748034d