Figure 3.

In silico functional analyses for rs385076 within the NLRC4 gene region. Co-localization of IL-18 associated variants and regulatory and epigenetic features were investigated in the UCSC Genome Browser (genome-euro.ucsc.edu) using genome release hg19. Only SNPs with P-values <5×10⁻⁸ for the association with circulating IL-18 levels are shown (green track). Tracks showing histone modifications and PU.1 binding sites were uploaded into the UCSC Genome Browser from an external study²² (red tracks). The PU.1 track represents binding sites of the transcription factor PU.1 in monocytes from a CHIP-seq experiment. The H3K27ac track shows histone modification by acetylation from CHIP-seq experiments in monocytes, which can be considered as a mark for active enhancers²⁶. The H3K4me1 mark shows regions undergoing histone methylation, which are likely to reflect cell-type specific regulation of a gene²⁷. Enhancer regions are highlighted by DNaseI hypersensitivity clusters from the ENCODE project²¹. In the bottom track, CHIP-seq results for transcription factors (TF) from the ENCODE project are shown, indicating TF binding regions. rs385076 falls into the 5‘UTR exon of NLRC4 and a binding region of PU.1. DNase hypersensitivity clusters around rs385076 suggest a good DNA accessibility in monocytes and histone modification data highlights the region as an enhancer.