Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-18182
PROVIDER: PRJNA174034 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Expression profile of lung adenocarcinoma, A549 cells following induction of non metastatic 2 (NME2/NM23 H2)
| PRJNA173068 | ENA
Project description:Genome-wide maps of NME2 in A549 lung adenocarcinoma cells.
| PRJNA173992 | ENA
Project description:This SuperSeries is composed of the following subset Series: GSE18182: Expression profile of lung adenocarcinoma, A549 cells following targeted depletion of non metastatic 2 (NME2/NM23 H2) GSE18284: Genomic binding sites of non-metastatic 2 (NME2) across promoters in lung cancer A549 cells Refer to individual Series
2011-02-08 | E-GEOD-18285 | biostudies-arrayexpress
Project description:It is widely believed that reorganization of nucleosomes result in availability of binding sites that engage transcription factors during eukaryotic gene regulation. Recent findings, on the other hand, suggest that transcription factors induced as a result of physiological perturbations directly (or in association with chromatin modifiers) may alter nucleosome occupancy to facilitate DNA binding. Although, together these suggest a close relationship between transcription factor binding and nucleosome reorganization, the nature of the inter-dependency, or to what extent it influences regulatory transcription is not clear. Moreover, since most studies used physiolgical pertubations that induced multiple transcription factor chromatin modifiers, the relatively local (or direct) effect of transcription factor binding on nucleosome occupancy remains unclear. With these in mind, we used a single transcription factor to induce physiological changes, representing metastatic (aggressive cancer) and the corresponding non-metastatic state, in human cancer cells. Following characterization of the two states (before and after induction of the transcription factor) we determined: (a) genome wide binding sites of the transcription factor, (b) promoter nucleosome occupancy and (c) transcriptome profiles, independently in both conditions. Interestingly, we find only ~20% of TF binding results from nucleosome reorganization - however, almost all corresponding genes were transcriptionally altered. Whereas, in cases where TF-occupancy was independent of nucleosome repositioning (in close vicinity), or co-occurred with nucleosomes, only a small fraction of the corresponding genes were expressed/repressed. Together, these indicate a model where TF occupancy only when coupled with nucleosome repositioning in close proximity is transcriptionally active. This, to our knowledge, for the first time also helps explain why genome wide TF occupancy (e.g., from ChIP-seq) is typically associated with only a small fraction of genes that change expression. For expression profiling of cells in NME2-induced conditions, A549 cells were transfected with pcDNA-NME2-MYC or pcDNA-MYC (control). RNA was isolated from the cells 48h after transfection using the trizol method (Sigma) as per manufacturerM-bM-^@M-^Ys protocol. Total RNA was processed to hybridize to Illumina Human HT-12 v4 Expression BeadChip as per manufacturerM-bM-^@M-^Ys instructions. Three biological replicates were averaged and data was analyzed using BeadStudio (P <0.05 of fold change).
2014-08-04 | E-GEOD-40194 | biostudies-arrayexpress
Project description:Non-metastatic 2 (NME2) is an established metastases suppressor in multiple human cancer types. However, the molecular mechanisms of NME2 action remain insufficiently resolved. We recently validated the transcription regulatory activity of NME2 with respect to control of proto-oncogene c-MYC expression. We hypothesized that large scale transcriptional potential of NME2 may be at the core of metastases suppression by NME2. Using a combination of high throughput genomic assays such as chromatin immunoprecipitation coupled to promoter array hybridization (ChIP-chip) and gene expression profiling, we characterized the transcriptional roles of NME2. Specifically, we found a set of NME2 target genes which changed expression upon selective depletion of NME2 in a lung cancer cell line, A549. The analysis of gene expression suggested control of various biological pathways esp. cell adhesion and apoptosis by NME2 target genes which could be important in regulation of metastases. For transcriptome analysis, total RNA was purified from A549 cells transiently silenced for NME2 (siRNA duplex against NME2/ NM23 H2(Santa Cruz)) or transfected with control siRNA duplexes. Isolated RNA was converted to cDNA, transcribed in vitro to synthesize biotinylated cRNA, and hybridized to Affymetrix HG-U133 plus 2.0 GeneChip oligonucleotide microarrays, according to manufacturer’s instructions. Three biological replicates were averaged and significance analysis performed using GCOS (P <0.005 of fold change).
2011-02-08 | E-GEOD-18182 | biostudies-arrayexpress
Project description:Genomic binding sites of non-metastatic 2 (NME2) across promoters in lung cancer A549 cells
| PRJNA123513 | ENA
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature