Ontology highlight
ABSTRACT:
PROVIDER: PRJNA656397 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12426578.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:Ewing sarcoma is a bone malignancy of children and young adults, frequently harboring the EWS/FLI t(11;22)(q24;q12) chromosomal translocation. The resulting fusion protein is an aberrant transcription factor that uses highly repetitive GGAA-containing elements (microsatellites) to activate and repress thousands of target genes mediating oncogenesis. However, the mechanisms of EWS/FLI interaction with microsatellites and regulation of target genes expression is not clearly understood. Here, we profile genome-wide protein binding and gene expression. Using a combination of unbiased genome-wide computational and experimental analysis, we define GGAA-microsatellites in a Ewing sarcoma context. Our study identifies two distinct classes of GGAA-microsatellites and demonstrates that EWS/FLI responsiveness is dependent on microsatellite length. At close range (within 5 kb) “promoter-like” microsatellites, EWS/FLI binding and subsequent target genes activation is highly dependent on the number of GGAA-motifs. “Enhancer-like” microsatellites demonstrate a positive correlation with length-dependent EWS/FLI binding, but minimal correlation for activated and none for repressed target genes. Our data suggest that EWS/FLI binds to “promoter-like” and “enhancer-like” microsatellites to mediate activation and repression of target genes through different regulatory mechanisms. Such characterization contributes valuable insight to EWS/FLI transcription factor biology and clarifies the role of GGAA-microsatellites on a global genomic scale. This may provide a unique perspective on the role of non-coding DNA in cancer susceptibility and therapeutic development.
2017-11-09 | GSE99959 | GEO
Project description:The purpose of this study was to evaluate a set of 6-7 long oligonucleotide probes developed based on the sequence of the Populus trichocarpa genome, that are optimal for gene expression analysis of P. deltoides and a hybrid of P. deltoides and P. trichocarpa. To evaluate these probes, multiple tissues (differentiating xyle, leaf and whole-root) of a pure P. deltoides and a hybrid (P. deltoides X P. trichocarpa) were transcript profiled for identification of one or more probes that are not biased towards one or the other genotype.
2008-09-10 | GSE12492 | GEO
Project description:Ewing sarcoma usually expresses the EWS/FLI fusion transcription factor oncoprotein. EWS/FLI regulates myriad genes required for Ewing sarcoma development. EWS/FLI binds GGAA-microsatellite sequences in vivo and in vitro, and these sequences provide EWS/FLI-mediated activation to reporter constructs, suggesting that they function as EWS/FLI-response elements. Genomic GGAA-microsatellites are highly variable and polymorphic. Current data suggest that there is an optimal “sweet-spot” GGAA-microsatellite length (of 18-26 GGAA repeats) that confers maximal EWS/FLI-responsiveness to target genes, but the mechanistic basis for this was not known. We now demonstrate the absolute necessity of an EWS/FLI-bound GGAA-microsatellite in regulation of the NR0B1 gene, as well as for Ewing sarcoma proliferation and oncogenic transformation. Biochemical studies, using recombinant Δ22 (a version of EWS/FLI containing only the FLI portion) demonstrated a stoichiometry of one Δ22-monomer binding to every two consecutive GGAA-repeats on shorter GGAA-microsatellite sequences. Surprisingly, the affinity for Δ22 binding to GGAA-microsatellites significantly decreased, and ultimately became unmeasureable, when the size of the GGAA-microsatellite was increased to the “sweet-spot” length. In contrast, a fully-functional EWS/FLI mutant (Mut9) that retains approximately half of the EWS portion of the fusion showed low affinity for smaller GGAA-microsatellites, but instead significantly increased its affinity at “sweet-spot” microsatellite lengths. Single-gene ChIP and genome-wide ChIP-seq and RNA-seq studies extended these findings to the in vivo setting. Taken together, these data demonstrate the absolute requirement of GGAA-microsatellites as EWS/FLI activating response elements in vivo and reveal an unsuspected novel role for the EWS portion of the EWS/FLI fusion in binding to optimal-length GGAA-microsatellites.
2017-10-22 | GSE94480 | GEO
Project description:A microarray analysis of whole-genome gene expression in roots was carried out in a (Populus trichocarpa X Populus deltoides) X Populus deltoides pseudo-backcross pedigree. Genetic variation in gene expression was quantified for 55,793 predicted gene models based on a single probe per gene. Resultant data contributed to the analysis of the genetic architecture of gene expression in roots of Populus. Data include one biological replicate of 163 individuals segregating from a pseudo-backcross pedigree of (Populus trichocarpa X Populus deltoides) X Populus deltoides analyzed for gene expression (GE) in roots using one probe per gene for 55793 independent gene models (probes E_POPLARSxxxxxPxxxxx) and single feature sequence polymorphism (SFP) using one probe per gene for 12084 independent gene models (probes G_POPLARSxxxxxPxxxxx). GE and SFP probes were selected from 6-7 probes per gene previously tested in a pilot study of the two parent trees of the cross (Populus deltoides X Populus trichocarpa)
2010-06-24 | E-GEOD-20118 | biostudies-arrayexpress