Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA389719 | ENA |
REPOSITORIES: ENA
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Project description:Genome-scale Activation Screen Identifies a LncRNA Locus Regulating a Gene Neighborhood
| PRJNA389741 | ENA
Project description:Genome-scale Activation Screen Identifies a LncRNA Locus Regulating a Gene Neighborhood [ChIP-Seq]
| PRJNA389746 | ENA
Project description:Long noncoding RNAs (lncRNAs) have been implicated in controlling various aspects of embryonic stem cell (ESC) biology, although the functions of specific lncRNAs, and the molecular mechanisms through which they act, remain unclear. Here, we demonstrate discrete and opposing roles for the lncRNA transcript Haunt and its genomic locus in regulating the HOXA gene cluster during ESC differentiation. Reducing or enhancing Haunt expression, with minimal disruption of the Haunt locus, led to up- or down-regulation of HOXA genes, respectively. In contrast, increasingly large genomic deletions within the Haunt locus attenuated HOXA activation. The Haunt DNA locus contains potential enhancers of HOXA activation, whereas Haunt RNA acts to prevent aberrant HOXA expression. This work reveals a multi-faceted model of lncRNA-mediated transcriptional regulation of the HOXA cluster, with distinct roles for a lncRNA transcript and its genomic locus, while illustrating the power of rapid CRISPR/Cas9-based genome editing for assigning lncRNA functions. All RNA-seq(s) were designed to reveal the differentially expressed genes among different stages of ESCs differentiation, or differentially expressed genes between wild-type or Haunt or HOXA mutant cells during RA-induced differentiation. All ChIRP-Seq were used to reveal the DNA or RNA targets of Haunt before or after RA treatment.
2015-04-20 | E-GEOD-58514 | biostudies-arrayexpress
Project description:SARS-CoV-2 causes the COVID-19 pandemic. It is urgent to develop disease models to dissect mechanisms regulating SARS-CoV-2 infection. Here, we derive airway organoids from human pluripotent stem cells (hPSC-AOs). The hPSC-AOs, particularly ciliated-like cells, are permissive to SARS-CoV-2 infection. Using this platform, we perform a high content screen and identify GW6471, which blocks SARS-CoV-2 infection. GW6471 can also block infection of the B.1.351 SARS-CoV-2 variant. RNA-seq analysis suggests that GW6471 blocks SARS-CoV-2 infection at least in part by inhibiting HIF1α, which is further validated by chemical inhibitor and genetic perturbation targeting HIF1α. Metabolic profiling identifies decreased rates of glycolysis upon GW6471 treatment, consistent with transcriptome profiling. Finally, xanthohumol, 5-(Tetradecyloxy)-2-furoic acid, and ND-646, three compounds that suppress fatty acid biosynthesis, also block SARS-CoV-2 infection. Together, a high content screen coupled with transcriptome and metabolic profiling reveals a key role of the HIF1α-glycolysis axis in mediating SARS-CoV-2 infection of human airway epithelium.
2021-09-24 | ST001921 | MetabolomicsWorkbench
Project description:Long noncoding RNAs (lncRNAs) have been implicated in controlling various aspects of embryonic stem cell (ESC) biology, although the functions of specific lncRNAs, and the molecular mechanisms through which they act, remain unclear. Here, we demonstrate discrete and opposing roles for the lncRNA transcript Haunt and its genomic locus in regulating the HOXA gene cluster during ESC differentiation. Reducing or enhancing Haunt expression, with minimal disruption of the Haunt locus, led to up- or down-regulation of HOXA genes, respectively. In contrast, increasingly large genomic deletions within the Haunt locus attenuated HOXA activation. The Haunt DNA locus contains potential enhancers of HOXA activation, whereas Haunt RNA acts to prevent aberrant HOXA expression. This work reveals a multi-faceted model of lncRNA-mediated transcriptional regulation of the HOXA cluster, with distinct roles for a lncRNA transcript and its genomic locus, while illustrating the power of rapid CRISPR/Cas9-based genome editing for assigning lncRNA functions.
2015-04-20 | GSE58514 | GEO
Project description:The CDKN2A/B locus at 9p21.3 contains crucial tumor suppressor (P16, P14, and P15) and oncogenic lncRNA ANRIL genes. This locus is most frequently inactivated in cancer genomes by deletion and DNA methylation. However, the mechanisms coordinately regulating their expression level are far from clear. In the present study, a novel lncRNA, P14AS, was characterized in the antisense strand of the fragment near CDKN2A exon1 in human cell lines using CDKN2A-specific probe captured RNA-sequencing (RNACap-Seq).
2019-03-07 | GSE127905 | GEO
Project description:The CDKN2A/B locus at 9p21.3 contains crucial tumor suppressors (P16, P14, and P15) and oncogenic lncRNA ANRIL genes. This locus is most frequently inactivated in cancer genomes by deletion and DNA methylation. However, the mechanisms coordinately regulating their expression level are far from clear. In the present study, a novel lncRNA, P14AS, was characterized in the antisense strand of the fragment near CDKN2A in human cell lines using CDKN2A-specific probe captured RNA-sequencing (RNACap-Seq).
2019-03-13 | GSE128205 | GEO
Project description:Among the large, diverse set of mammalian long noncoding RNAs (lncRNAs), long noncoding primary microRNAs (lnc-pri-miRNAs) are those that host miRNAs. Whether lnc-pri-miRNA loci have important biological function independent of their cognate miRNAs is poorly understood. From a genome-scale lncRNA screen, lnc-pri-miRNA loci were enriched for function in cell proliferation, and in glioblastoma (i.e., GBM) cells with DGCR8 or DROSHA knockdown, lnc-pri-miRNA screen hits still regulated cell growth. To molecularly dissect the function of a lnc-pri-miRNA locus, we studied LOC646329 (also known as MIR29HG), which hosts the miR-29a/b1 cluster. In GBM cells, LOC646329 knockdown reduced miR-29a/b1 levels, and these cells exhibited decreased growth. However, genetic deletion of the miR-29a/b1 cluster (LOC646329-miR29Δ) did not decrease cell growth, while knockdown of LOC646329-miR29Δ transcripts reduced cell proliferation. The miR-29a/b1-independent activity of LOC646329 corresponded to enhancer-like activation of a neighboring oncogene (MKLN1), regulating cell propagation. The LOC646329 locus interacts with the MKLN1 promoter, and antisense oligonucleotide knockdown of the lncRNA disrupts these interactions and reduces the enhancer-like activity. More broadly, analysis of genome-wide data from multiple human cell types showed that lnc-pri-miRNA loci are significantly enriched for DNA looping interactions with gene promoters as well as genomic and epigenetic characteristics of transcriptional enhancers. Functional studies of additional lnc-pri-miRNA loci demonstrated cognate miRNA-independent enhancer-like activity. Together, these data demonstrate that lnc-pri-miRNA loci can regulate cell biology via both miRNA-dependent and miRNA-independent mechanisms.
2021-03-12 | GSE137048 | GEO
Project description:Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging [RNA-seq]
| PRJNA733455 | ENA
Project description:Using a combination of chromatin capture techniques, ChIP-Seq, single-molecule in situ RNA analysis, and computational analysis of large-scale TCGA datasets, we identified an epigenetic mechanism underlying common activation of HOXD/miR-10b locus in otherwise highly heterogenous glioma brain tumors. We demonstrate for the first time that two remote lncRNAs, one associated with a genomic promoter and another with a newly identified enhancer, cooperatively shape the 3D chromatin structure and looping, leading to the activation of a large gene cluster (12 genes, 110 KB) that includes the regulatory miRNA essential for glioma survival. This work describes a new mechanism contributing to neoplastic transformation in gliomagenesis, and identifies new avenues for therapeutic interventions based on the promoter and enhancer associated regulatory transcripts.
2021-11-11 | GSE161257 | GEO