Epigenetic Atlas of Bladder Cancer Reveals Master Transcription Factors and Risk-Associated Regulatory Elements in Luminal and Basal-Squamous Molecular Subtypes

We performed histone ChIP-seq, the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq), and RNA sequencing (RNA-seq) on 28 fresh frozen bladder/upper tract tumor samples. We integrated 64 unique data sets to gain a holistic view of gene regulation in bladder cancer expression/molecular subtypes and nominated candidate subtype-specific master transcription factors (TF) driving expression differences. We also integrated bladder GWAS risk SNPs with H3K27ac ChIP-seq and ATAC-seq data and revealed that risk variants were significantly enriched in genetically determined peaks Overall design: We performed histone ChIP-seq, ATAC-seq, and RNA sequencing (RNA-seq) to annotate the epigenetic landscape then integrate that data to nominate candidate master TFs important to maintain cellular identity. We also GWAS risk loci with epigenetically marked peaks.