Shared genetic effects on chromatin and gene expression reveal widespread enhancer priming in immune response

摘要: Noncoding regulatory variants are often highly context-specific, modulating gene expression in a small subset of possible cellular states. Although these genetic effects likely to play important roles disease, the molecular mechanisms underlying context-specificity not well understood. Here, we identify shared quantitative trait loci (QTLs) for chromatin accessibility and (eQTLs) show that large fraction (~60%) eQTLs appear following macrophage immune stimulation alter unstimulated cells, suggesting they perturb enhancer priming. We such influence binding cell type specific transcription factors (TFs), as PU.1, which then indirectly stimulus-specific TFs, NF-κB or STAT2. Our results imply that, although assays powerful fine mapping causal noncoding variants, detecting their downstream impact on will be challenging, requiring profiling numbers stimulated states timepoints.