Fig. 4
Functional annotation of neutrophil-specific hypervariable CpG positions. a Enrichment of neutrophil-specific HVPs (n = 261) at genomic features. We found neutrophil-specific HVPs to be depleted at CpG islands (P = 6.37 × 10−19, hypergeometric test). b Enrichment of neutrophil-specific HVPs at gene elements. Neutrophil-specific HVPs were enriched at intergenic regions (P = 0.03). c Enrichment of neutrophil-specific HVPs at distinct reference chromatin states in neutrophils. The HVPs were enriched at enhancer (P = 1.32 × 10−12) and “variable” (P = 3.81 × 10−8) chromatin states. A variable chromatin state denotes a state that was observed in less than 80% of the biological replicates (n ≥ 5) within a given cell type and indicates dynamic changes of local chromatin structure. d Regional plot of an exemplar neutrophil-specific HVP mapping to the promoter of the ITGB1BP1 gene, encoding the integrin beta 1 binding protein 1. The statistically significant HVP is indicated with an arrowhead. For each cell type, data points represent the DNA methylation β values (y-axis) at the indicated CpGs (x-axis) in one individual. For each CpG site, we calculated the mean DNA methylation value (indicated with a larger data point). Every CpG site is annotated with regards to genomic feature, gene element, and chromatin state. Abbreviations: M monocytes, N neutrophils, T naïve T cells, TSS transcription start site, CGI CpG island, UTR untranslated region, prom promoter