Fig. 5: The rs748670681 variant affects the transcription of the TNRC18 and WIPI2 genes. | Nature Communications

Fig. 5: The rs748670681 variant affects the transcription of the TNRC18 and WIPI2 genes.

From: A genome-wide CRISPR screen identifies the TNRC18 gene locus as a regulator of inflammatory signaling

Fig. 5: The rs748670681 variant affects the transcription of the TNRC18 and WIPI2 genes.The alternative text for this image may have been generated using AI.

a UCSC genome browser view of the TNRC18 gene locus. Tracks from top to bottom show RefSeq protein coding genes, H3K4Me1, H3K4Me3, and H3K27Ac marks in human macrophage cells from the BLUEPRINT Project. The rs748670681 variant, located inside intron 2 of TNRC18, is marked with a red triangle. The minor, risk-associated T allele of rs748670681 diminishes luciferase reporter gene expression in Jurkat (b) and Caco-2 (c) cells compared to the common, non-risk allele C. Statistical significance was determined using two-sided, unpaired Student’s t test (*P < 0.05). d Target sequence for HDR-mediated CRISPR-Cas9 editing of the rs748670681 variant sequence. e Editing was performed in three independent experiments and quantified using next-generation sequencing with at least 50 K sequencing reads. Normalized expression values of the WIPI2 (f) and TNRC18 (g) transcripts in cells edited with CRISPR-Cas9 to be homozygous for the T allele of rs748670681. Each bar in graphs represents mean of replicates ± SD (n = 9). Statistical significance was determined using two-sided, unpaired Student’s t test (*P < 0.05). H3K4Me1 histone H3 lysine 4 monomethylation, H3K4Me3 histone H3 lysine 4 trimethylation, H3K27Ac histone H3 lysine 27 acetylation, CPM counts per million, Luc luciferase, PAM protospacer adjacent motif, LPS lipopolysaccharide.

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