Integrative multi-omic analysis identifies key transcription factors and target proteins in renal cell carcinoma and its subtypes.

ABSTRACT: To characterize key transcription factors (TFs) whose differential DNA binding can be altered by genetic variants associated with risk for renal cell carcinoma (RCC), we conducted a series of mixed model-based analyses integrating 449 TF ChIP-seq profiles across 9 kidney-related cell lines and summary statistics from a multi-ancestry genome-wide association study of RCC. We identified 96 unique TFs for which presence of SNPs in a neighborhood of TF ChIP-seq peaks are significantly associated (p-value <1×10-4) with their effect on RCC, including EPAS1, ARNT, PAX8 and PBRM1, previously implicated in RCC pathogenesis. Most TFs overlapped active promoters/enhancers in RCC tumors but remained significant after adjusting for tumor chromatin accessibility. Further, we found the co-occupancy of 22

SUBMITTER: Chhetri SB 

PROVIDER: S-EPMC12703995 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature