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Rewiring of master transcription factor cistrome during high-grade serous ovarian cancer development [Hi-C]

ABSTRACT: Rewiring of master transcription factor cistrome during high-grade serous ovarian cancer development [Hi-C]

PROVIDER: PRJNA954375 | ENA |

REPOSITORIES: ENA

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

Project description:Rewiring of master transcription factor cistrome during high-grade serous ovarian cancer development

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Rewiring of master transcription factor cistrome during high-grade serous ovarian cancer development [RNA-seq]

Project description:Rewiring of master transcription factor cistrome during high-grade serous ovarian cancer development [RNA-seq]

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

Project description: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 and survival but only depletion of PAX8 and WT1 impaired FTSEC cell survival. These four TFs were pharmacologically inhibited by transcriptional inhibitors only in HGSCs but not in FTSECs. Collectively, our data highlights that tumor-specific epigenetic remodeling is tightly related to MECOM, PAX8, SOX17 and WT1 activity and these transcription factors are targetable in a tumor-specific manner through transcriptional inhibitors.

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Rewiring of master transcription factor cistrome during high-grade serous ovarian cancer development [Hi-C]

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Epigenomic remodeling of the PAX8 cistrome in high grade serous ovarian cancer [ChIP-Seq]

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Epigenomic remodeling of the PAX8 cistrome in high grade serous ovarian cancer [RNA-Seq]

Project description:We report mapping of the PAX8 cistrome in three high grade serous ovarian cancer cell lines (KURAMOCHI, OVSAHO, and JHOS4) compared to three benign immortalized fallopian tube cell lines (FT33, FT194, and FT246). We identified a highly conserved PAX8 binding pattern common across benign fallopian tube cell lines that was distinct from the unique PAX8 binding patterns seen in each cancer cell line. Comparison of benign and malignant Mullerian cell lines with and without PAX8 knockdown. For each cell line, three distinct siRNAs targeting PAX8 plus a pool of all three siRNAs were examined and compared to both a non-transfected control as well as a control transfected with a non-targeting siRNA.

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Epigenomic remodeling of the PAX8 cistrome in high grade serous ovarian cancer

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