Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays

Abstract

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.

Figure 1

Genes up-regulated by IFNs. The probe sets from hybridized oligonucleotide arrays corresponding to the indicated IFN-induced genes are represented. 9–27 is an example of a gene that is regulated by all IFNs. IRF-1 is preferentially induced by IFN-γ. 2–5A-Synthetase (1.8 kb mRNA; 2–5AS) is induced selectively by IFN-α and -β, but not IFN-γ. HIF-1α is selectively induced by IFN-β. Perfect-match oligonucleotides are tiled across the upper rows of each boxed probe set while corresponding single-base mismatch oligonucleotides are tiled across the lower rows.