Genetic landscape and functional exploration of kidney cancer predisposition causality in cross-ancestral populations [ATAC-seq]

To functionally explore renal cell carcinoma (RCC) susceptibility variants, we performed CUT&Tag for H3K27ac and ATAC-seq on 769P cells to assess transcriptional activity. Subsequently, we conducted a CRISPR screen and CRISPR droplet sequencing (CROP-seq), which combines pooled CRISPR screens with single-cell RNA sequencing (scRNA-seq), to identify target genes potentially regulated by likely causal SNPs. Functionally, we established a novel association between rs28684409 and the oncogene RPL4 at the complex genetic locus 15q22.31. As the next step, we performed CRISPRi on rs28684409 and conducted RNA-seq to identify differential gene expression associated with this variant. Overall design: ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) in renal cancer cell line 769P. This experiment focuses on identifying open chromatin regions, revealing the accessibility of regulatory elements and their potential role in transcriptional regulation.