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

中文翻译：

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转录因子 NF-κB 在对 Toll 样受体 4 信号传导的初级反应期间协调核小体重塑

数百个潜在增强子和几个启动子的诱导核小体重塑塑造了巨噬细胞中对 Toll 样受体 4 (TLR4) 信号传导的转录反应。我们的目的是确定促进 TLR 诱导重塑的转录因子的身份。基于 ATAC-seq 和单细胞 ATAC-seq 的分析策略富集了最有可能经历重塑的基因组区域，结果表明转录因子核因子 κB (NF-κB) 与原代期间标记重塑的所有高置信度峰结合。对 TLR4 配体脂质 A 的反应。NF-κB 亚基 RelA 和 c-Rel 的缺失导致高置信度 ATAC-seq 峰处的重塑丢失，并且 NF-κB 结合基序的 CRISPR-Cas9 突变会损害重塑。特定区域的重塑选择性是通过与其他诱导因子（包括 IRF3 和 MAP 激酶诱导因子）的协作而赋予的。因此，NF-κB 在 TLR4 激活的转录因子中是独一无二的，因为它对诱导型核小体重塑具有广泛的贡献，并且能够激活组装成开放染色质的平衡增强子和启动子。