Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays.
The pleiotropic activities of interferons (IFNs) are mediated primarily through the transcriptional regulation of many downstream effector genes. The mRNA profiles from IFN-alpha, -beta, or -gamma treatments of the human fibrosarcoma cell line, HT1080, were determined by using oligonucleotide arrays with probe sets corresponding to more than 6,800 human genes. Among these were transcripts for known IFN-stimulated genes (ISGs), the expression of which were consistent with previous studies in which the particular ISG was characterized as responsive to either Type I (alpha, beta) or Type II (gamma) IFNs, or both. Importantly, many novel IFN-stimulated genes were identified that were diverse in their known biological functions. For instance, several novel ISGs were identified that are implicated in apoptosis (including RAP46/Bag-1, phospholipid scramblase, and hypoxia inducible factor-1alpha). Furthermore, several IFN-repressed genes also were identified. These results demonstrate the usefulness of oligonucleotide arrays in monitoring mammalian gene expression on a broad and unprecedented scale. In particular, these findings provide insights into the basic mechanisms of IFN actions and ultimately may contribute to better therapeutic uses for IFNs.
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Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Zhou
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Williams
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Silverman
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D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004798:Enzymes / Q000276:immunology*; D005354:Fibrosarcoma; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016898:Interferon-alpha / Q000494:pharmacology / Q000502:physiology*; D016899:Interferon-beta / Q000494:pharmacology / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D015345:Oligonucleotide Probes; D049294:Phospholipid Transfer Proteins; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004798:Enzymes; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016898:Interferon-alpha; D008565:Membrane Proteins; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D049294:Phospholipid Transfer Proteins; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016899:Interferon-beta; D007371:Interferon-gamma