Homo sapiens Transcriptome or Gene expression

Here, we describe a strategy in which candidate functional risk variants are evaluated using genome-editing to create isogenic cell lines representing all possible genotypes. We created a panel of isogenic 22Rv1 prostate cancer cell lines representing all three rs339331 genotypes (TT, TC, CC). The risk allele causally increased transcription of the RFX6 gene, increased HOXB13 binding, and increased deposition of the enhancer-associated H3K4me2 histone mark. The cell lines also differed in cellular morphology: TT cells were more adhesive than the CC cells consistent with a cancer-related phenotype. Pathway analysis of differentially expressed genes between the CC and TTlines was predicted to be androgen regulated, a key pathway in prostatecancer biology.