Faculty, Staff and Student Publications
Publication Date
1-21-2023
Journal
Nature Communications
Abstract
While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays. We integrate 153 individual data sets from 42 patients and nominate 50 histology-specific master transcription factors (MTF) to define RCC histologic subtypes, including EPAS1 and ETS-1 in ccRCC, HNF1B in pRCC, and FOXI1 in chRCC. We confirm histology-specific MTFs via immunohistochemistry including a ccRCC-specific TF, BHLHE41. FOXI1 overexpression with knock-down of EPAS1 in the 786-O ccRCC cell line induces transcriptional upregulation of chRCC-specific genes, TFCP2L1, ATP6V0D2, KIT, and INSRR, implicating FOXI1 as a MTF for chRCC. Integrating RCC GWAS risk SNPs with H3K27ac ChIP-seq and ATAC-seq data reveals that risk-variants are significantly enriched in allelically-imbalanced peaks. This epigenomic atlas in primary human samples provides a resource for future investigation.
Keywords
Humans, Carcinoma, Renal Cell, Kidney Neoplasms, Epigenomics, Transcription Factors, Oncogenes, Forkhead Transcription Factors
DOI
10.1038/s41467-023-35833-5
PMID
36681680
PMCID
PMC9867739
PubMedCentral® Posted Date
January 2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Neoplasms Commons, Nephrology Commons, Oncology Commons
Comments
Associated Data
PMID: 36681680