Abstract
Macrophages play a critical role in inflammatory responses during infections. Activated macrophages by infections through stimulation of TLRs expressed their cell surface produce pro-inflammatory cytokines, including TNF. However, distal enhancers that regulate TNF gene transcription in human macrophages have not been investigated. In this study, we identified the five putative TNF enhancers using H3K27ac ChIP-seq and ATAC-seq. We showed proximal enhancer (PE), E-16.0, and E-6.5 possessed enhancer activity in a reporter gene assay. Deletion of the distal TNF E-16.0 enhancer resulted in 73% reduction in TNF gene transcription in human macrophage cell line THP-1 in response to ploy(I:C) stimulation. Our study identifies a novel distal enhancer that regulates TNF gene transcription in human macrophages.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Grant support: Supported by grants from the National Institutes of Health R01AI107022 and R01AI083986 (H.H.).