Fig. 2: Multiple eQTL SNPs at 17q12 locus are potential causal variants and involved in the regulation of HNF1B expression. | Nature Communications

Fig. 2: Multiple eQTL SNPs at 17q12 locus are potential causal variants and involved in the regulation of HNF1B expression.

From: Extensive germline-somatic interplay contributes to prostate cancer progression through HNF1B co-option of TMPRSS2-ERG

Fig. 2

a Eleven of the thirteen SNPs in the HNF1B region were found to have significant eQTL association with HNF1B isoform 1 expressed in prostate glands (n = 466). The SNP rs11986220 within the 8q24 region was used as a non-relevant control site for the analysis. HNF1B-001 (NCBI source: NM_000458); HNF1B-003 (NCBI source: NM_001165923); HNF1B-004 (NCBI source: NM_001304286). Genotype to gene expression correlations were assessed with linear regression. b The 17q12/HNF1B locus eQTL analysis of genes within 1-Mbp region using the Wisconsin cohort of benign prostate tissues (n = 466). c RT-qPCR analysis to determine the mRNA expression levels of HNF1B in 22Rv1 cells with partial knockout (KO) of each SNP region or dampened HNF1B via CRISPR/Cas9 genome editing technology. n = 15 samples; P values based on the order of appearance: 7,39E–05, 3,6E–04, 3,8E–03, 6,8E–04, 1E–03, 1,7E–04, 3,14E–05, 9,29E–05, 1,8E–04, 8,08E–05, 6,59E–05, 1,5E–04, 6,46E–05, 1,44E–05. d Reporter assays on six SNP regions with different alleles and in both orientations (5‘−3’, 3‘−5’) showing contribution of each region as an enhancer for HNF1B promoter in 22Rv1. Prom: Promoter. n = 25 samples; P values based on the order of appearance: 0,025, 0,589, 0,402, 0,17, 0,024, 0,085, 8,9E–03, 0,016, 0,071, 2E–04, 0,038, 6,1E–04, 0,091, 0,268, 0,22, 0,602, 9,5E–04, 6,1E–04, 9,4E–03, 7,1E–03, 2E–03, 8,6E–03, 8,1E–03, 0,035. e RT-qPCR analysis of HNF1B expression levels in 22Rv1 cell clones with CRISPR/Cas9-mediated deletion of each SNP region. Two independent clones were isolated for analysis from each KO-population. n = 14 samples; P values based on the order of appearance: 4,4E–05, 5,1E–05, 9,4E–05, 5E–05, 4,9E–05, 2,5E–05, 2E–04, 1,5E–04, 3E–04, 2,8E–03, 2,7E–05, 2,6E–05. In (c–e), n = 3 technical replicates, error bars, mean ± SD, * P < 0.05, ** P < 0.01, *** P < 0.001, ns: non-significant, P values were evaluated using the two-tailed Student’s t tests. Source data are provided in Source Data file.

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