The transcription factor NF-κB orchestrates nucleosome remodeling during the primary response to Toll-like receptor 4 signaling

• DOI: 10.1016/j.immuni.2024.02.004
• Publication Date: 2024-03-01T15:31:09Z
• Authors: An-Chieh Feng; Brandon J. Thomas; Prabhat K. Purbey; Filipe Menegatti ...; Xin Liu; Allison E. Daly; Fei Sun; Jerry Hung-Hao Lo; Lijing Cheng; Michael F. Carey; Philip O. Scumpia; Stephen T. Smale
• Keywords: Transcription

Inducible nucleosome remodeling at hundreds of latent enhancers and several promoters shapes the transcriptional response to Toll-like receptor 4 (TLR4) signaling in macrophages. We aimed define identities transcription factors that promote TLR-induced remodeling. An analysis strategy based on ATAC-seq single-cell enriched for genomic regions most likely undergo revealed factor nuclear κB (NF-κB) bound all high-confidence peaks marking during primary TLR4 ligand, lipid A. Deletion NF-κB subunits RelA c-Rel resulted loss peaks, CRISPR-Cas9 mutagenesis NF-κB-binding motifs impaired Remodeling selectivity defined was conferred by collaboration with other inducible factors, including IRF3- MAP-kinase-induced factors. Thus, is unique among TLR4-activated its broad contribution remodeling, alongside ability activate poised assembled into open chromatin.