Human Alu loci gain enhancer-type epigenetic modifications in monocytes during response to bacterial LPS.

backgroundBacterial lipopolysaccharide (LPS) potently activates innate immunity. Transposable elements (TEs), particularly lineage-specific short interspersed elements (SINEs), have been implicated in immune regulatory evolution, yet their epigenomic roles during immune activation remain unclear.

resultsHere, we reanalyzed published ChIP-seq data for H3K4me1, H3K4me3, and H3K27ac from human monocytes and mouse macrophage-like cells under basal and LPS-stimulated conditions. We identified widespread and dynamic activation of Alu-associated regulatory regions in human monocytes, accounting for around 15% of total enhancer-associated ChIP-seq peaks with and without LPS stimulation. In particular, over one quarter of the Alu-containing H3K4me1 and H3K27ac peaks appeared only after LPS stimulation. The Alu-containing enhancers that appeared in short treatment with LPS linked to many genes involved in the acute immune and inflammatory responses. On the other hand, prolonged LPS stimulation produced stronger chromatin activation at Alu loci that were linked to genes with more dispersed pathway associations, likely reflecting post-stimulation adaptation or tolerance.

conclusionsThese findings suggest that Alu elements act as regulatory scaffolds that shape the temporal and functional landscape of human immune responses. Our findings suggest that Alu elements, as primate-specific TEs, may contribute to heightened sensitivity to LPS by shaping species-specific enhancer landscapes.