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NF-kB Broadly Orchestrates Nucleosome Remodeling during the Primary Response to Toll-Like Receptor 4 Signaling [scATAC-seq]

ABSTRACT: Inducible nucleosome remodeling at hundreds of latent enhancers and several promoters helps shape the transcriptional response to Toll-like receptor 4 (TLR4) signaling in macrophages. However, the identities of the transcription factors that promote TLR-induced remodeling have remained elusive. An analysis strategy that enriched ATAC-seq profiles for genomic regions most likely to undergo remodeling uncovered a unique relationship between NF-kB and TLR4-induced remodeling events. A critical functional role for NF-kB in remodeling was then revealed by CRISPR-Cas9 mutagenesis of NF-kB genes and binding motifs. This critical role is broad and possibly universal during the TLR4 primary response. Remodeling selectivity at defined regions is often conferred by collaboration between NF-kB and other inducible factors, including IRF3 and MAP kinase-induced factors. Thus, NF-kB is unique among TLR4-induced transcription factors in its broad contribution to inducible nucleosome remodeling, alongside its well-established ability to activate poised enhancers and promoters assembled into open chromatin.

ORGANISM(S): Mus musculus

PROVIDER: GSE248713 | GEO | 2024/01/16

REPOSITORIES: GEO

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