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Satellite repeat RNA expression in epithelial ovarian cancer is linked to a tumor immunosuppressive phenotype

ABSTRACT: Satellite repeat RNA expression in epithelial ovarian cancer is linked to a tumor immunosuppressive phenotype

PROVIDER: PRJNA845211 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19537800_1.fastq.gz	Fastqsanger.gz
	SRR19537800_2.fastq.gz	Fastqsanger.gz
	SRR19537801_1.fastq.gz	Fastqsanger.gz
	SRR19537801_2.fastq.gz	Fastqsanger.gz
	SRR19537802_1.fastq.gz	Fastqsanger.gz

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Satellite repeat RNA expression in epithelial ovarian cancer is linked to a tumor immunosuppressive phenotype

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Project description:Aberrant transcription of the HSATII pericentromeric satellite repeat is present in a wide variety of epithelial cancers. We observed that HSATII expression is induced in colon cancer cells cultured as xenografts or under non-adherent conditions in vitro, but it is rapidly lost in standard 2D cultures. Unexpectedly, physiological induction of endogenous HSATII RNA, as well as introduction of synthetic HSATII transcripts, generate complementary DNA intermediates in the form of DNA:RNA hybrids. Single molecule sequencing of tumor xenografts shows that HSATII RNA-derived DNA (rdDNA) molecules are stably reincorporated within pericentromeric loci, leading to progressive expansion of these regions We analyzed the dynamics of HSATII RNA and DNA level changes using single molecule sequencing (Helicos/SeqLL) in SW620 colon cancer cells transitioned from 2D in vitro culture conditions to growth as mouse xenografts and vice versa.

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Project description:Repetitive sequences, transposable elements and silent tissue-specific genes in C. elegans are differentially enriched for di- and tri-methyl H3 lysine 9 (H3K9). SET-25 (SUV39h1/h2) catalyzes H3K9me3, while MET-2 (SetDB1) deposits only H3K9me1/me2. RNA-seq and genome-wide H3K9 methylation mapping in met-2 and set-25 single mutants showed that H3K9me2-mediated repression of satellite repeats by MET-2 correlates with germline integrity. Aberrant transcription of repeats and DNA transposons generates R-loops, loss of fertility and hydroxyurea hypersensitivity. In a genome-wide synthetic lethal screen, we identified the BRCA1 complex and factors implicated in the degradation of nuclear RNA as essential for germline integrity in met-2 mutants. Highly additive with met-2, the loss of the BRCA1 complex triggers satellite repeat transcription, generating R-loops on transcribed repeats. Supporting direct causality between satellite repeat transcription and BRCA1-mediated genome integrity, the targeted induction of MSAT1 transcripts at endogenous sites leads to damage-induced loss of fertility in wild-type C. elegans.

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Satellite Cells

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FOXD3 acts as a repressor of repeat elements in a heterochromatin-mediated pathway

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