Ontology highlight
ABSTRACT:
PROVIDER: PRJNA655844 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12407570_1.fastq.gz | Fastqsanger.gz | |||
| SRR12407570_2.fastq.gz | Fastqsanger.gz | |||
| SRR12407571_1.fastq.gz | Fastqsanger.gz | |||
| SRR12407571_2.fastq.gz | Fastqsanger.gz | |||
| SRR12407572_1.fastq.gz | Fastqsanger.gz |
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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.
2023-05-12 | GSE227779 | GEO
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.
2023-05-01 | GSE229408 | GEO
Project description:Activation of lineage-specific gene expression programs is mediated by the sequence-specific recruitment of transcriptional coactivators to chromatin. This occurs via interaction with lineage specific DNA binding transcription factors. The lineage factor PAX8 drives essential gene expression in ovarian cancer cells and is required for tumor proliferation. However, the molecular details surrounding co-factor recruitment and specific activation of transcription by PAX8 remain unknow. Here, we identify an important functional interaction between PAX8 and the Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. We show that PAX8 can recruit SWI/SNF complexes to DNA, where they function to open chromatin and facilitate expression of PAX8 target genes. Genetic deletion of PAX8 results in loss of SWI/SNF from PAX8 bound enhancers, loss of expression of associated target genes, and reduced proliferation. These results can be phenocopied by pharmacological inhibition of SWI/SNF ATPase activity. These data indicate that PAX8 mediates the expression of an essential ovarian cancer proliferative program in part by the recruitment of chromatin remodelers.
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Project description:Activation of lineage-specific gene expression programs is mediated by the sequence-specific recruitment of transcriptional coactivators to chromatin. This occurs via interaction with lineage specific DNA binding transcription factors. The lineage factor PAX8 drives essential gene expression in ovarian cancer cells and is required for tumor proliferation. However, the molecular details surrounding co-factor recruitment and specific activation of transcription by PAX8 remain unknow. Here, we identify an important functional interaction between PAX8 and the Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. We show that PAX8 can recruit SWI/SNF complexes to DNA, where they function to open chromatin and facilitate expression of PAX8 target genes. Genetic deletion of PAX8 results in loss of SWI/SNF from PAX8 bound enhancers, loss of expression of associated target genes, and reduced proliferation. These results can be phenocopied by pharmacological inhibition of SWI/SNF ATPase activity. These data indicate that PAX8 mediates the expression of an essential ovarian cancer proliferative program in part by the recruitment of chromatin remodelers.
2024-08-04 | GSE272992 | GEO
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.
2016-08-08 | E-GEOD-79893 | biostudies-arrayexpress
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.
2016-08-08 | GSE79893 | GEO
Project description:Critical developmental “master transcription factors” (MTFs) can be subverted during tumorigenesis to control expression of oncogenic transcriptional programs. Current approaches to identify MTFs rely on chromatin immunoprecipitation-sequencing data, which is currently unavailable for many cancer types. We developed the CaCTS (Cancer Core Transcription factor Specificity) algorithm to prioritize candidate MTFs using pan-cancer RNA-sequencing data. CaCTS identified candidate MTFs across 34 tumor types and 140 subtypes, including known MTFs. We also made novel predictions, including for cancer types/subtypes for which MTFs are unknown. This included PAX8, SOX17, and MECOM as candidate MTFs in ovarian cancer (OV). In OV cells, these factors are required for viability, lie proximal to super-enhancers, co-occupy regulatory elements globally and co-bind at critical gene loci encoding OV biomarkers. Identification of tumor MTFs, especially for tumor types with limited understanding of transcriptional drivers, paves the way to therapeutic targeting of MTFs in a broad spectrum of cancers.
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Project description:Estrogen Receptor alpha (ERα) is a key driver of most breast cancers, and it is the target of endocrine therapies used in the clinic to treat women with ERα positive (ER+) breast cancer. The two methods ChIP-seq (chromatin immunoprecipitation coupled with deep sequencing) and RIME (Rapid Immunoprecipitation of Endogenous Proteins) have greatly improved our understanding of ERα function during breast cancer progression and in response to anti-estrogens. A critical component of both ChIP-seq and RIME protocols is the antibody that is used to pull down the bait protein. To date, most of the ChIP-seq and RIME experiments for the study of ERα have been performed using the sc-543 antibody from Santa Cruz Biotechnology. However, this antibody has been discontinued, thereby severely impacting the study of ERα in normal physiology as well as diseases such as breast cancer and ovarian cancer. Here, we compare the sc-543 antibody with other commercially available antibodies, and we show that 06-935 (EMD Millipore) and ab3575 (Abcam) antibodies can successfully replace the sc-543 antibody for ChIP-seq and RIME experiments.
2019-03-21 | PXD012930 | Pride
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.
2016-08-08 | E-GEOD-83100 | biostudies-arrayexpress