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Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome

ABSTRACT: Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome

PROVIDER: PRJNA835865 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19128823.fastq.gz	Fastqsanger.gz
	SRR19128824.fastq.gz	Fastqsanger.gz
	SRR19128825.fastq.gz	Fastqsanger.gz
	SRR19128826.fastq.gz	Fastqsanger.gz
	SRR19128827.fastq.gz	Fastqsanger.gz

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Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome

Project description:In this study, we reveal insights into the biogenesis of downstream-of-gene (DoG)-containing RNAs in human cancers.

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TT-TL-seq reveals transcriptional profiles that accompany DoG induction after hyperosmotic stress.

Project description:TT-TimeLapse-seq was used to investigate the nascent transcription profiles that accompany the induction of downstream-of-gene (DoG) containing transcripts in human cell lines. Data from HEK-293T cells exposed to hyperosmotic stress and cells transfected with siRNAs against Integrator subunit 11 are included.

2021-01-04 | GSE152059 | GEO

Hyperosmotic stress induces downstream-of-gene transcription and alters the RNA Polymerase II interactome despite widespread transcriptional repression

Project description:Stress-induced readthrough transcription results in the synthesis of thousands of downstream-of-gene (DoG) containing transcripts. The mechanisms underlying DoG formation during cellular stress remain unknown. Nascent transcription profiles during DoG induction in human cell lines using TT-TimeLapse-seq revealed that hyperosmotic stress induces widespread transcriptional repression. Yet, DoGs are produced regardless of the transcriptional level of their upstream genes. ChIP-seq confirmed that the stress-induced redistribution of RNA Polymerase (Pol) II correlates with the transcriptional output of genes. Stress-induced alterations in the Pol II interactome are observed by mass spectrometry. While subunits of the cleavage and polyadenylation machinery remained Pol II-associated, Integrator complex subunits dissociated from Pol II under stress conditions. Depleting the catalytic subunit of the Integrator complex, Int11, using siRNAs induces hundreds of readthrough transcripts, whose parental genes partially overlap those of stress-induced DoGs. Our results provide insights into the mechanisms underlying DoG production and how Integrator activity influences DoG transcription. This SuperSeries is composed of the SubSeries listed below.

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Gene expression from beagle dog mandible

Project description:In this study, beta-TCP was implanted in dog mandibles, after which the gene expression profiles and signaling pathways were monitored using microarray and Ingenuity Pathways Analysis (IPA). Following the extraction of premolars and subsequent bone healing, betaâTCP was implanted into the artificial osseous defect. Total RNA was isolated from bone tissues and gene expression profiles were examined using microarray analysis. We used microarrays to detail the global programme of gene expression and identified distinct classes of up- and down- regulated genes during this process. Waiting 3 months healing after tooth extraction from beagle dog mandibles, we drilled the holes in the dog mandibles, and implanted without and with beta-TCP. And these dog mandibles were selected for RNA extraction and hybridization on Affymetrix microarrays. After implanting beta-TCP in the dog mandibles 4, 7, 14 days, we selected sample at 3 time points: Control_4d, beta-TCP_4d, Control_7d, beta-TCP_7d, Control_14d, beta-TCP_14d.

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Allelic imbalance is a prevalent and tissue-specific feature of the mouse transcriptome

Project description:We perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ~20% of the mouse transcriptome. Allelic imbalance attributed to genotype is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5’ and 3’ termini of transcripts. We further identify novel random monoallelic and imprinted genes, and find that genotype can compete with parental origin even in the setting of large imprinted regions. PolyA-selected RNA-sequencing in F1 hybrid and parental cells of Mm. musculus and Mm. castaneus origin

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Transmissible Dog Cancer

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Dog sequences

Project description:Candidate study of dog genes

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Gene expression profiling of human and dog breast cancers

Project description:Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Keywords: Expression profiling by array

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RNA polymerase II pausing downstream of core histone genes is different from genes producing polyadenylated transcripts

Project description:Recent genome-wide chromatin immunoprecipitation coupled high throughput sequencing (ChIP-seq) analyses performed in various eukaryotic organisms, analysed RNA Polymerase II (Pol II) pausing around the transcription start sites of genes. In this study we have further investigated genome-wide binding of Pol II downstream of the 3' end of the annotated genes (EAGs) by ChIP-seq in human cells. At almost all expressed genes we observed Pol II occupancy downstream of the EAGs suggesting that Pol II pausing 3' from the transcription units is a rather common phenomenon. Downstream of EAGs Pol II transcripts can also be detected by global run-on and sequencing, suggesting the presence of functionally active Pol II. Based on Pol II occupancy downstream of EAGs we could distinguish distinct clusters of Pol II pause patterns. On core histone genes, coding for non-polyadenylated transcripts, Pol II occupancy is quickly dropping after the EAG. In contrast, on genes, whose transcripts undergo polyA tail addition [poly(A)+], Pol II occupancy downstream of the EAGs can be detected up to 4-6 kb. Inhibition of polyadenylation significantly increased Pol II occupancy downstream of EAGs at poly(A)+ genes, but not at the EAGs of core histone genes. The differential genome-wide Pol II occupancy profiles 3' of the EAGs have also been confirmed in mouse embryonic stem (mES) cells, indicating that Pol II pauses genome-wide downstream of the EAGs in mammalian cells. Moreover, in mES cells the sharp drop of Pol II signal at the EAG of core histone genes seems to be independent of the phosphorylation status of the C-terminal domain of the large subunit of Pol II. Thus, our study uncovers a potential link between different mRNA 3' end processing mechanisms and consequent Pol II transcription termination processes. Examination of RNA Polymerase II in MCF-7 cell line

2012-06-15 | E-GEOD-34001 | biostudies-arrayexpress

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