MYC and HSF1 Cooperate to Drive PLK1 inhibitor Sensitivity in High Grade Serous Ovarian Cancer
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PROVIDER: PRJNA1130486 | ENA |
REPOSITORIES: ENA
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Project description:MYC and HSF1 genes are amplified in approximately 1/3 of ovarin cancer patients. However, their molecular interactions and cooperation to drive ovarian cancer has not been studied nor has their DNA binding patterns been compared in ovarian cancer cells. This project studies the interactions between MYC and HSF1 in ovarian cancer cells, including identifying their binding patterns across the genome for comparison. Ovarian cancer cells with MYC-HSF1 co-amplification (OVCAR8) underwent CUT&RUN for IgG, MYC, and HSF1 followed by sequencing.
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Project description:Heat shock transcription factors HSF1 and HSF2 both are necessary for proper spermatogenesis, which is disrupted at elevated temperatures. We studied how HSF1 and HSF2 cooperate during the heat shock response in mouse spermatocytes. For this purpose we used ChIP-sequencing. ChIP-Seq analyses revealed that the temperature elevation induces remodeling of HSF1 and HSF2 binding to chromatin. The highest HSF1-chromatin binding was observed at 43°C, when HSF2-chromatin binding was reduced. Many promoters (mainly Hsp genes) were occupied by both heat shock factors at physiological temperature of testes and/or at 38°C. In contrary at 43°C only HSF1 was bound. Obtained results suggest that HSF1 and HSF2 could cooperate in regulation of the transcription of some genes only at physiological temperatures and/or at 38°C. Alteration in HSFs interactions and their binding to chromatin could be one of the reason of increased spermatogenic cell death observed after heat shock.
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Project description:Low-grade serous ovarian carcinomas are typically Ras-pathway mutated, TP53 wild-type, have limited chromosomal aberration, and are frequently associated with borderline tumors. By contrast, high-grade serous ovarian carcinoma lack Ras-pathway mutations, are invariably TP53 mutated, show widespread genomic change, and are commonly BRCA-pathway disrupted. We sought to identify differences in genomic copy number changes in borderline and invasive components of serous carcinoma.
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Project description:Low-grade serous ovarian carcinomas are typically Ras-pathway mutated, TP53 wild-type, have limited chromosomal aberration, and are frequently associated with borderline tumors. By contrast, high-grade serous ovarian carcinoma lack Ras-pathway mutations, are invariably TP53 mutated, show widespread genomic change, and are commonly BRCA-pathway disrupted. We sought to identify differentially expressed genes between co-existing borderline and invasive components of serous carcinoma.
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