Rewiring of master transcription factor cistromes during high-grade serous ovarian cancer development.

ABSTRACT: The transcription factors MECOM, PAX8, SOX17 and WT1 are candidate master regulators of high-grade serous 'ovarian' cancer (HGSC), yet their cooperative role in the hypothesized tissue of origin, the fallopian tube secretory epithelium (FTSEC) is unknown. We generated 26 epigenome (CUT&TAG, CUT&RUN, ATAC-seq and HiC) data sets and 24 profiles of RNA-seq transcription factor knock-down followed by RNA sequencing in FTSEC and HGSC models to define binding sites and gene sets regulated by these factors in cis and trans. This revealed that MECOM, PAX8, SOX17 and WT1 are lineage-enriched, super-enhancer associated master regulators whose cooperative DNA-binding patterns and target genes are re-wired during tumor development. All four TFs were indispensable for HGSC clonogenicity a

SUBMITTER: Nameki RA 

PROVIDER: S-EPMC10120620 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature