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• W4307446588 abstract "ABSTRACT Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is an essential and evolutionarily conserved transcription factor complex primarily involved in innate immunity and inflammation. Transposable elements (TEs) can be co-opted to innovate immune transcriptional regulatory networks; however, the extent to which TEs have contributed to the modulation of NF-κB response in different mammalian lineages is not well established. Here we performed a multi-species analysis of TEs bound by the NF-κB subunit RELA (p65) in response to the pro-inflammatory cytokine TNFα (Tumor Necrosis Factor alpha). Using endothelial cell RELA ChIP-seq data from human, mouse and cow, we found that 55 TE subfamilies were enriched within NF-κB bound regions. These RELA-bound transposons possess multiple active epigenetic features and reside near TNFα-induced genes. A prominent example of lineage-specific contribution of transposons comes from the bovine SINE subfamilies Bov-tA1/2/3 which collectively contributed over 14,000 NF-κB bound regions in cow. By comparing NF-κB binding data across species, we found several examples of NF-κB motif-bearing TEs that appeared to colonize the genome prior to the divergence of the selected mammals, including a DNA transposon MER81, whose ancestral sequence contains two intact RELA motifs. We demonstrate that one NF-κB bound MER81 element can control the TNFα-induced expression of INFGR2 (Interferon Gamma Receptor 2) in human. Lastly, the presence of RELA motifs within MER81 elements appeared to stabilize during human evolution, indicative of purifying selection acting on a subset of these NF-κB bound ancient DNA transposons. Taken together, our results implicate multiple transposons in establishing NF-κB mediated regulatory networks during mammalian evolution." @default.
• W4307446588 created "2022-11-01" @default.
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• W4307446588 date "2022-10-26" @default.
• W4307446588 modified "2023-10-02" @default.
• W4307446588 title "Multi-species analysis of inflammatory response elements reveals ancient and lineage-specific contributions of transposable elements to NF-κB binding" @default.
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