Characterization of Basal and Estrogen-Regulated Antisense Transcription in Breast Cancer Cells: Role in Regulating Sense Transcription
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE140210 | GEO | 2022/08/02
REPOSITORIES: GEO
Similar Datasets
Project description:<p>High throughput RNA Sequencing has revealed that the human genome is widely transcribed. However, the extent of natural antisense transcription, the molecular mechanisms by which natural antisense transcripts (NATs) might affect their cognate sense genes, and the role of NATs in cancer are less well understood. Here, we use strand-specific paired-end RNA sequencing (ssRNASeq) on a cohort of 376 cancer patients covering 9 tissue types to comprehensively characterize the landscape of antisense expression. Our results reveal that greater than 60% of annotated transcripts have measureable antisense expression and the expression of sense and antisense transcript pairs is in general positively correlated. Furthermore, by studying the expression of sense/antisense pairs across tissues we identify lineage-specific, ubiquitous and cancer-specific antisense loci. Our results raise the possibility that NATs participate in the regulation of well-known tumor suppressors and oncogenes. Finally, this study provides a catalogue of cancer related genes with significant antisense transcription (oncoNAT). This resource will allow researchers to investigate the molecular mechanisms of sense/antisense regulation and further advance our understanding of their role in cancer.</p>
| phs000937 | dbGaP
Project description:Comparison of sense (forward probes) and antisense (reverse probes on U74 v1 gene arrays) transcripts in mouse kidney and brain. Positive calls related to antisense transcripts were compared to the cognate signals on the 430 version of mouse genome arrays to obtain genes that co expressed sense and antisense transcripts. This had to be done manually because divergent probe IDs on the two chip generations. Experiment Overall Design: The first Affymetrix U74 mouse gene chips contains reversely oriented probe sets. These probes will hybridize to natural antisense transcripts that overlap with the sense transcript in the cognate area. Affymetrix provided a mask to identify the reverse probes. Positive calls with these reverse probes will give an estimate of the antisense transcriptome in that particular tissue. Comparison of the reversely oriented probes with correctly annotated probes will reveal the expression ratio of sense and antisense transcripts.
2008-06-14 | E-GEOD-6106 | biostudies-arrayexpress
Project description:Comparison of sense (forward probes) and antisense (reverse probes on U74 v1 gene arrays) transcripts in mouse kidney and brain. Positive calls related to antisense transcripts were compared to the cognate signals on the 430 version of mouse genome arrays to obtain genes that co expressed sense and antisense transcripts. This had to be done manually because divergent probe IDs on the two chip generations. Keywords: Qualitative comparison of expression
2006-11-07 | GSE6106 | GEO
Project description:High throughput RNA sequencing has revealed pervasive transcription of human genome than previously anticipated. However, the extent of natural antisense transcripts (NATs) expression, their regulation of cognate sense genes, and the role of NATs in cancer remain poorly understood. Here, we use strand-specific paired-end RNA sequencing (ssRNASeq) data from 376 cancer patients covering 9 tissue types to comprehensively characterize the landscape of antisense expression. We found consistent antisense expression in at least 38% of annotated transcripts, which in general is positively correlated with sense gene expression. Investigations of sense/antisense pair expression across tissue types revealed lineage-specific, ubiquitous and cancer-specific antisense loci transcription. Comparisons between tumor and normal samples identified both concordant (same direction) and discordant (opposite direction) sense/antisense expression patterns. Finally, we provide oncoNAT, a catalog of cancer related genes with significant antisense transcription, which will enable future investigations of sense/antisense regulation in cancer. Using oncoNAT we identified several functional NATs, including NKX2-1-AS that regulates the NKX2-1 oncogene and cell proliferation in lung cancer cells. Overall, this study provides a comprehensive account of NATs and supports a role for NATs regulation of tumor suppressors and oncogenes in cancer biology. Strand-specific RNA sequencing data (ssRNASeq) of cancer and benign samples. SRP048484 (PRJNA262128).
2015-05-28 | E-GEOD-66727 | biostudies-arrayexpress
Project description:High throughput RNA sequencing has revealed pervasive transcription of human genome than previously anticipated. However, the extent of natural antisense transcripts (NATs) expression, their regulation of cognate sense genes, and the role of NATs in cancer remain poorly understood. Here, we use strand-specific paired-end RNA sequencing (ssRNASeq) data from 376 cancer patients covering 9 tissue types to comprehensively characterize the landscape of antisense expression. We found consistent antisense expression in at least 38% of annotated transcripts, which in general is positively correlated with sense gene expression. Investigations of sense/antisense pair expression across tissue types revealed lineage-specific, ubiquitous and cancer-specific antisense loci transcription. Comparisons between tumor and normal samples identified both concordant (same direction) and discordant (opposite direction) sense/antisense expression patterns. Finally, we provide oncoNAT, a catalog of cancer related genes with significant antisense transcription, which will enable future investigations of sense/antisense regulation in cancer. Using oncoNAT we identified several functional NATs, including NKX2-1-AS that regulates the NKX2-1 oncogene and cell proliferation in lung cancer cells. Overall, this study provides a comprehensive account of NATs and supports a role for NATs regulation of tumor suppressors and oncogenes in cancer biology.
2015-05-28 | GSE66728 | GEO
Project description:High throughput RNA sequencing has revealed pervasive transcription of human genome than previously anticipated. However, the extent of natural antisense transcripts (NATs) expression, their regulation of cognate sense genes, and the role of NATs in cancer remain poorly understood. Here, we use strand-specific paired-end RNA sequencing (ssRNASeq) data from 376 cancer patients covering 9 tissue types to comprehensively characterize the landscape of antisense expression. We found consistent antisense expression in at least 38% of annotated transcripts, which in general is positively correlated with sense gene expression. Investigations of sense/antisense pair expression across tissue types revealed lineage-specific, ubiquitous and cancer-specific antisense loci transcription. Comparisons between tumor and normal samples identified both concordant (same direction) and discordant (opposite direction) sense/antisense expression patterns. Finally, we provide oncoNAT, a catalog of cancer related genes with significant antisense transcription, which will enable future investigations of sense/antisense regulation in cancer. Using oncoNAT we identified several functional NATs, including NKX2-1-AS that regulates the NKX2-1 oncogene and cell proliferation in lung cancer cells. Overall, this study provides a comprehensive account of NATs and supports a role for NATs regulation of tumor suppressors and oncogenes in cancer biology.
2015-05-28 | GSE66727 | GEO
Project description:High throughput RNA sequencing has revealed pervasive transcription of human genome than previously anticipated. However, the extent of natural antisense transcripts (NATs) expression, their regulation of cognate sense genes, and the role of NATs in cancer remain poorly understood. Here, we use strand-specific paired-end RNA sequencing (ssRNASeq) data from 376 cancer patients covering 9 tissue types to comprehensively characterize the landscape of antisense expression. We found consistent antisense expression in at least 38% of annotated transcripts, which in general is positively correlated with sense gene expression. Investigations of sense/antisense pair expression across tissue types revealed lineage-specific, ubiquitous and cancer-specific antisense loci transcription. Comparisons between tumor and normal samples identified both concordant (same direction) and discordant (opposite direction) sense/antisense expression patterns. Finally, we provide oncoNAT, a catalog of cancer related genes with significant antisense transcription, which will enable future investigations of sense/antisense regulation in cancer. Using oncoNAT we identified several functional NATs, including NKX2-1-AS that regulates the NKX2-1 oncogene and cell proliferation in lung cancer cells. Overall, this study provides a comprehensive account of NATs and supports a role for NATs regulation of tumor suppressors and oncogenes in cancer biology. Strand-specific RNA sequencing data (ssRNASeq) of cancer and benign samples. SRP050021 (PRJNA267614). Processed data files linked to SuperSeries record.
2015-05-28 | E-GEOD-66728 | biostudies-arrayexpress
Project description:Transcription is typically divergent, initiating at closely spaced oppositely oriented core promoters to produce sense and unstable upstream antisense transcripts (uasTrx). How antisense transcription is regulated and coordinated with sense transcription is largely unknown. Here by combining acute degradation of the multi-functional transcription factor CTCF and nascent transcription measurements, we find that CTCF specifically suppresses antisense but not sense transcription at hundreds of divergent promoters, the great majority of which bear proximal CTCF binding sites. Genome editing, chromatin conformation studies and 5’ transcript mapping revealed that CTCF directly suppresses uasTrx initiation in manner independent of its chromatin architectural function. Primary transcript RNA FISH revealed co-bursting of sense and anti-sense transcripts is disfavored, suggesting CTCF-regulated competition for transcription initiation. In sum, CTCF shapes the noncoding transcriptional landscape by suppressing upstream antisense transcription.
2022-05-02 | GSE173443 | GEO
Project description:Transcription is typically divergent, initiating at closely spaced oppositely oriented core promoters to produce sense and unstable upstream antisense transcripts (uasTrx). How antisense transcription is regulated and coordinated with sense transcription is largely unknown. Here by combining acute degradation of the multi-functional transcription factor CTCF and nascent transcription measurements, we find that CTCF specifically suppresses antisense but not sense transcription at hundreds of divergent promoters, the great majority of which bear proximal CTCF binding sites. Genome editing, chromatin conformation studies and 5’ transcript mapping revealed that CTCF directly suppresses uasTrx initiation in manner independent of its chromatin architectural function. Primary transcript RNA FISH revealed co-bursting of sense and anti-sense transcripts is disfavored, suggesting CTCF-regulated competition for transcription initiation. In sum, CTCF shapes the noncoding transcriptional landscape by suppressing upstream antisense transcription.
2022-05-02 | GSE173442 | GEO
Project description:Demonstration of a massive lncRNA RNA transcriptional program in the mammalian genome has engendered lively discussions about their biological roles, particularly the promoter antisense (PAS) transcripts of coding gene transcription units and abundant species localized to specific subnuclear structures with phase separation properties. Here, we report development of an alternative assay to quantitatively detect RNA distribution in the genome, referred to as ChIRC-seq (Chromatin Isolation by RNA-Cas13a Complex Capture by Cas13a), which has revealed that promoter antisense RNAs (PAS-RNAs) serve as a key gatekeeper of a broad transcriptional pause release program, based on decommissioning the 7SK snRNA-dependent inhibitory P-TEFb complex. Induction of PAS-RNA by liganded estrogen receptor ERα (ESR1) releases the basal recruitment of HP1α and KAP1 on target gene promoters, without the spreading characteristic of extended heterochromatic regions, based on PAS-dependent recruitment of H3K9me3 demethylases. Unexpectedly, ERα-bound MegaTrans enhancer activation with features of phase separation events proved to require recruitment of phosphorylated KAP1 to be activated, with its transfer to the cognate promoters licensing estrogen-induced pause release and target gene activation. The ChIRC13a-seq method has proved effective for identification of the cognate promoter for activated enhancers and has revealed that the lncRNAs NEAT1/MALAT1 in phase-separated subnuclear structures interact with robust estrogen-activated MegaTrans TFF1e1 enhancer and other active enhancers, linking acute activation of a subset of enhancers to interactions with specific phase-separated subnuclear architectural structures.
2021-03-24 | GSE163494 | GEO