Similar Datasets
Project description:Nuclear speckles are dynamic nuclear bodies characterized by high local concentrations of RNA binding proteins and specific non-coding RNAs. Although the contents of speckles suggest multifaceted roles in regulating chromatin dynamics and gene expression, the overarching biological function(s) of nuclear speckles remain enigmatic. In this study, we investigate speckle compositional variation in human cancer, finding two main speckle compositional states based on RNA expression of speckle-resident proteins. One cancer speckle state was more similar to normal adjacent tissues, while the other was dissimilar from normal tissue, and thus considered an aberrant cancer speckle state. We link the aberrant speckle state to altered speckle positioning within the nucleus, to elevation of the TREX RNA export complex, and to worse patient outcomes in clear cell renal cell carcinoma (ccRCC). ccRCC is typified by hyperactivation of the HIF-2a transcription factor, and we demonstrate that HIF-2a drives physical association of a select subset of its target genes with nuclear speckles depending on HIF-2a's two speckle targeting motifs (STMs) defined in this study. STMs are highly enriched among transcription factors, suggesting that DNA-speckle targeting may be a general mechanism of gene regulation and providing a resource of candidate speckle-targeting factors. Via integration of tissue culture functional studies with tumor genomic and imaging analysis, we show that HIF-2a gene regulatory programs are impacted by speckle compositional state and by abrogation of speckle targeting abilities of HIF-2a. These findings suggest that, in ccRCC, a key biological function of nuclear speckles is to modulate expression of a specific subset of HIF-2a-regulated target genes that, in turn, influence patient outcomes. Beyond ccRCC, tumor speckle compositional states broadly correlate with altered functional pathways and expression of speckle-associated gene neighborhoods, exposing a general link between nuclear speckles and gene expression dysregulation in human cancer.
2024-09-03 | GSE248706 | GEO
Project description:Nuclear speckles are dynamic nuclear bodies characterized by high local concentrations of RNA binding proteins and specific non-coding RNAs. Although the contents of speckles suggest multifaceted roles in regulating chromatin dynamics and gene expression, the overarching biological function(s) of nuclear speckles remain enigmatic. In this study, we investigate speckle compositional variation in human cancer, finding two main speckle compositional states based on RNA expression of speckle-resident proteins. One cancer speckle state was more similar to normal adjacent tissues, while the other was dissimilar from normal tissue, and thus considered an aberrant cancer speckle state. We link the aberrant speckle state to altered speckle positioning within the nucleus, to elevation of the TREX RNA export complex, and to worse patient outcomes in clear cell renal cell carcinoma (ccRCC). ccRCC is typified by hyperactivation of the HIF-2a transcription factor, and we demonstrate that HIF-2a drives physical association of a select subset of its target genes with nuclear speckles depending on HIF-2a's two speckle targeting motifs (STMs) defined in this study. STMs are highly enriched among transcription factors, suggesting that DNA-speckle targeting may be a general mechanism of gene regulation and providing a resource of candidate speckle-targeting factors. Via integration of tissue culture functional studies with tumor genomic and imaging analysis, we show that HIF-2a gene regulatory programs are impacted by speckle compositional state and by abrogation of speckle targeting abilities of HIF-2a. These findings suggest that, in ccRCC, a key biological function of nuclear speckles is to modulate expression of a specific subset of HIF-2a-regulated target genes that, in turn, influence patient outcomes. Beyond ccRCC, tumor speckle compositional states broadly correlate with altered functional pathways and expression of speckle-associated gene neighborhoods, exposing a general link between nuclear speckles and gene expression dysregulation in human cancer.
2024-09-03 | GSE248705 | GEO
Project description:Nuclear speckles are dynamic nuclear bodies characterized by high local concentrations of RNA binding proteins and specific non-coding RNAs. Although the contents of speckles suggest multifaceted roles in regulating chromatin dynamics and gene expression, the overarching biological function(s) of nuclear speckles remain enigmatic. In this study, we investigate speckle compositional variation in human cancer, finding two main speckle compositional states based on RNA expression of speckle-resident proteins. One cancer speckle state was more similar to normal adjacent tissues, while the other was dissimilar from normal tissue, and thus considered an aberrant cancer speckle state. We link the aberrant speckle state to altered speckle positioning within the nucleus, to elevation of the TREX RNA export complex, and to worse patient outcomes in clear cell renal cell carcinoma (ccRCC). ccRCC is typified by hyperactivation of the HIF-2a transcription factor, and we demonstrate that HIF-2a drives physical association of a select subset of its target genes with nuclear speckles depending on HIF-2a's two speckle targeting motifs (STMs) defined in this study. STMs are highly enriched among transcription factors, suggesting that DNA-speckle targeting may be a general mechanism of gene regulation and providing a resource of candidate speckle-targeting factors. Via integration of tissue culture functional studies with tumor genomic and imaging analysis, we show that HIF-2a gene regulatory programs are impacted by speckle compositional state and by abrogation of speckle targeting abilities of HIF-2a. These findings suggest that, in ccRCC, a key biological function of nuclear speckles is to modulate expression of a specific subset of HIF-2a-regulated target genes that, in turn, influence patient outcomes. Beyond ccRCC, tumor speckle compositional states broadly correlate with altered functional pathways and expression of speckle-associated gene neighborhoods, exposing a general link between nuclear speckles and gene expression dysregulation in human cancer.
2024-09-03 | GSE248710 | GEO
Project description:Nuclear speckles are dynamic nuclear bodies characterized by high local concentrations of RNA binding proteins and specific non-coding RNAs. Although the contents of speckles suggest multifaceted roles in regulating chromatin dynamics and gene expression, the overarching biological function(s) of nuclear speckles remain enigmatic. In this study, we investigate speckle compositional variation in human cancer, finding two main speckle compositional states based on RNA expression of speckle-resident proteins. One cancer speckle state was more similar to normal adjacent tissues, while the other was dissimilar from normal tissue, and thus considered an aberrant cancer speckle state. We link the aberrant speckle state to altered speckle positioning within the nucleus, to elevation of the TREX RNA export complex, and to worse patient outcomes in clear cell renal cell carcinoma (ccRCC). ccRCC is typified by hyperactivation of the HIF-2a transcription factor, and we demonstrate that HIF-2a drives physical association of a select subset of its target genes with nuclear speckles depending on HIF-2a's two speckle targeting motifs (STMs) defined in this study. STMs are highly enriched among transcription factors, suggesting that DNA-speckle targeting may be a general mechanism of gene regulation and providing a resource of candidate speckle-targeting factors. Via integration of tissue culture functional studies with tumor genomic and imaging analysis, we show that HIF-2a gene regulatory programs are impacted by speckle compositional state and by abrogation of speckle targeting abilities of HIF-2a. These findings suggest that, in ccRCC, a key biological function of nuclear speckles is to modulate expression of a specific subset of HIF-2a-regulated target genes that, in turn, influence patient outcomes. Beyond ccRCC, tumor speckle compositional states broadly correlate with altered functional pathways and expression of speckle-associated gene neighborhoods, exposing a general link between nuclear speckles and gene expression dysregulation in human cancer.
2024-09-03 | GSE248709 | GEO
Project description:Nuclear speckles are dynamic nuclear bodies characterized by high local concentrations of RNA binding proteins and specific non-coding RNAs. Although the contents of speckles suggest multifaceted roles in regulating chromatin dynamics and gene expression, the overarching biological function(s) of nuclear speckles remain enigmatic. In this study, we investigate speckle compositional variation in human cancer, finding two main speckle compositional states based on RNA expression of speckle-resident proteins. One cancer speckle state was more similar to normal adjacent tissues, while the other was dissimilar from normal tissue, and thus considered an aberrant cancer speckle state. We link the aberrant speckle state to altered speckle positioning within the nucleus, to elevation of the TREX RNA export complex, and to worse patient outcomes in clear cell renal cell carcinoma (ccRCC). ccRCC is typified by hyperactivation of the HIF-2a transcription factor, and we demonstrate that HIF-2a drives physical association of a select subset of its target genes with nuclear speckles depending on HIF-2a's two speckle targeting motifs (STMs) defined in this study. STMs are highly enriched among transcription factors, suggesting that DNA-speckle targeting may be a general mechanism of gene regulation and providing a resource of candidate speckle-targeting factors. Via integration of tissue culture functional studies with tumor genomic and imaging analysis, we show that HIF-2a gene regulatory programs are impacted by speckle compositional state and by abrogation of speckle targeting abilities of HIF-2a. These findings suggest that, in ccRCC, a key biological function of nuclear speckles is to modulate expression of a specific subset of HIF-2a-regulated target genes that, in turn, influence patient outcomes. Beyond ccRCC, tumor speckle compositional states broadly correlate with altered functional pathways and expression of speckle-associated gene neighborhoods, exposing a general link between nuclear speckles and gene expression dysregulation in human cancer.
2024-09-03 | GSE248708 | GEO
Project description:Nuclear speckles are dynamic nuclear bodies characterized by high local concentrations of RNA binding proteins and specific non-coding RNAs. Although the contents of speckles suggest multifaceted roles in regulating chromatin dynamics and gene expression, the overarching biological function(s) of nuclear speckles remain enigmatic. In this study, we investigate speckle compositional variation in human cancer, finding two main speckle compositional states based on RNA expression of speckle-resident proteins. One cancer speckle state was more similar to normal adjacent tissues, while the other was dissimilar from normal tissue, and thus considered an aberrant cancer speckle state. We link the aberrant speckle state to altered speckle positioning within the nucleus, to elevation of the TREX RNA export complex, and to worse patient outcomes in clear cell renal cell carcinoma (ccRCC). ccRCC is typified by hyperactivation of the HIF-2a transcription factor, and we demonstrate that HIF-2a drives physical association of a select subset of its target genes with nuclear speckles depending on HIF-2a's two speckle targeting motifs (STMs) defined in this study. STMs are highly enriched among transcription factors, suggesting that DNA-speckle targeting may be a general mechanism of gene regulation and providing a resource of candidate speckle-targeting factors. Via integration of tissue culture functional studies with tumor genomic and imaging analysis, we show that HIF-2a gene regulatory programs are impacted by speckle compositional state and by abrogation of speckle targeting abilities of HIF-2a. These findings suggest that, in ccRCC, a key biological function of nuclear speckles is to modulate expression of a specific subset of HIF-2a-regulated target genes that, in turn, influence patient outcomes. Beyond ccRCC, tumor speckle compositional states broadly correlate with altered functional pathways and expression of speckle-associated gene neighborhoods, exposing a general link between nuclear speckles and gene expression dysregulation in human cancer.
2024-09-03 | GSE248707 | GEO
Project description:Nuclear speckles are membrane-less bodies within the cell nucleus enriched in RNA biogenesis, processing, and export factors. In this study we investigated speckle phenotype variation in human cancer, finding a reproducible speckle signature, based on RNA expression of speckle-resident proteins, across >20 cancer types. Of these, clear cell renal cell carcinoma (ccRCC) exhibited a clear correlation between the presence of this speckle expression signature, imaging-based speckle phenotype, and clinical outcomes. ccRCC is typified by hyperactivation of the HIF-2α transcription factor, and we demonstrate here that HIF-2α drives physical association of a select subset of its target genes with nuclear speckles. Disruption of HIF-2α-driven speckle association via deletion of its speckle targeting motifs (STMs)-defined in this study-led to defective induction of speckle-associating HIF-2α target genes without impacting non-speckle-associating HIF-2α target genes. We further identify the RNA export complex, TREX, as being specifically altered in speckle signature, and knockdown of key TREX component, ALYREF, also compromises speckle-associated gene expression. By integrating tissue culture functional studies with tumor genomic and imaging analysis, we show that HIF-2α gene regulatory programs are impacted by specific manipulation of speckle phenotype and by abrogation of speckle targeting abilities of HIF-2α. These findings suggest that, in ccRCC, a key biological function of nuclear speckles is to modulate expression of a specific subset of HIF-2α-regulated target genes that, in turn, influence patient outcomes. We also identify STMs in other transcription factors, suggesting that DNA-speckle targeting may be a general mechanism of gene regulation.
| S-EPMC10515914 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-06-24 | E-GEOD-68656 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-06-30 | GSE131466 | GEO
Project description:Nuclear speckles are dynamic nuclear bodies characterized by high local concentrations of RNA binding proteins and specific non-coding RNAs. Although the contents of speckles suggest multifaceted roles in regulating chromatin dynamics and gene expression, the overarching biological function(s) of nuclear speckles remain enigmatic. In this study, we investigate speckle compositional variation in human cancer, finding two main speckle compositional states based on RNA expression of speckle-resident proteins. One cancer speckle state was more similar to normal adjacent tissues, while the other was dissimilar from normal tissue, and thus considered an aberrant cancer speckle state. We link the aberrant speckle state to altered speckle positioning within the nucleus, to elevation of the TREX RNA export complex, and to worse patient outcomes in clear cell renal cell carcinoma (ccRCC). ccRCC is typified by hyperactivation of the HIF-2a transcription factor, and we demonstrate that HIF-2a drives physical association of a select subset of its target genes with nuclear speckles depending on HIF-2a's two speckle targeting motifs (STMs) defined in this study. STMs are highly enriched among transcription factors, suggesting that DNA-speckle targeting may be a general mechanism of gene regulation and providing a resource of candidate speckle-targeting factors. Via integration of tissue culture functional studies with tumor genomic and imaging analysis, we show that HIF-2a gene regulatory programs are impacted by speckle compositional state and by abrogation of speckle targeting abilities of HIF-2a. These findings suggest that, in ccRCC, a key biological function of nuclear speckles is to modulate expression of a specific subset of HIF-2a-regulated target genes that, in turn, influence patient outcomes. Beyond ccRCC, tumor speckle compositional states broadly correlate with altered functional pathways and expression of speckle-associated gene neighborhoods, exposing a general link between nuclear speckles and gene expression dysregulation in human cancer.
2024-09-03 | GSE269570 | GEO