Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Neutrophil transcript abundance following 3/6 hr culture in normoxia, hypoxia and anoxia

ABSTRACT: Neutrophils are key effector cells of the innate immune response and are required to migrate and function within highly adverse micro-environmental conditions. These inflammatory sites are characterised by low levels of oxygen. We examined the relative transcript abundance detected in an apoptosis targeted gene array following invitro neutrophil culture (3/6 hrs) in normoxic, hypoxic and anoxic conditions.

ORGANISM(S): Homo sapiens

SUBMITTER: Sarah Walmsley

PROVIDER: E-GEOD-968 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity.

Walmsley Sarah R SR Print Cristin C Farahi Neda N Peyssonnaux Carole C Johnson Randall S RS Cramer Thorsten T Sobolewski Anastasia A Condliffe Alison M AM Cowburn Andrew S AS Johnson Nicola N Chilvers Edwin R ER

The Journal of experimental medicine 20050101 1

Neutrophils are key effector cells of the innate immune response and are required to migrate and function within adverse microenvironmental conditions. These inflammatory sites are characterized by low levels of oxygen and glucose and high levels of reductive metabolites. A major regulator of neutrophil functional longevity is the ability of these cells to undergo apoptosis. We examined the mechanism by which hypoxia causes an inhibition of neutrophil apoptosis in human and murine neutrophils. W ...[more]

PMID: 15630139

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Project description:Alternative RNA splicing analysis in Hep3B cell cultured under 21% (N1,3,5) or 1.2% (H2,4,6) oxygen Hypoxia is a common characteristic of many solid tumors. The hypoxic microenvironment stabilizes hypoxia-inducible transcription factor 1? (HIF1?) and 2? (HIF2?) to activate gene transcription, which promotes tumor cell survival. 95% of human genes are alternatively spliced, producing RNA isoforms that code functionally distinct proteins. Thus, effective hypoxia response requires increased HIF target gene transcription as well as proper RNA splicing of these HIF target genes. However, it is unclear if and how hypoxia regulates RNA splicing of HIF target genes. This study determined the effects of hypoxia on alternative splicing (AS) of HIF and non-HIF target genes in Hep3B cells and characterized the role of HIF in regulating AS of HIF induced genes. The results indicated that hypoxia generally promotes exon inclusion for hypoxia-induced, but reduces exon inclusion for hypoxia reduced genes. Mechanistically, HIF activity, but not hypoxia per se is found to be necessary and sufficient to increase exon inclusion of several HIF target genes including pyruvate dehydrogenase kinase 1 (PDK1). PDK1 splicing reporters confirmed that transcriptional activation by HIF is sufficient to increase exon inclusion of PDK1 splicing reporter. In contrast, transcriptional activation of the PDK1 minigene by other transcription factor in the absence of endogenous HIF target gene activation fails to alter PDK1 RNA splicing, demonstrating a novel role of HIF target gene(s) in regulating RNA splicing of HIF target genes. Implications:This study demonstrates a novel function of HIF in regulating RNA splicing of HIF target genes. We analyzed total RNA from Hep3B cells cultured under 21% (N1,3,5) or 1.2% (H2,4,6) oxygen using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Altanalyze software version 2.0.7. Techinical replicates were performed for Nx and Hx treated Hep3B cells

Dataset Information

Neutrophil transcript abundance following 3/6 hr culture in normoxia, hypoxia and anoxia

Publications

Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity.

Similar Datasets

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