Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays.
Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays.
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DOI：
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发表时间：
1998
影响因子：
11.1
通讯作者：
S. Der;A. Zhou;B. Williams;R. Silverman
中科院分区：
文献类型：
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作者：
S. Der;A. Zhou;B. Williams;R. Silverman
干扰素（IFN）的多效活性主要是通过许多下游效应基因的转录调节来介导的。人类纤维肉瘤细胞系HT1080的IFN -ALPHA，-BETA或-GAMMA处理的mRNA谱是通过使用寡核苷酸阵列确定的，该寡核苷酸阵列的探针集对应于6,800多个人类基因。其中包括已知的IFN刺激基因（ISG）的转录本，其表达与以前的研究一致，在这些研究中，特定的ISG被表征为对I型（alpha，beta）或II型（gamma）IFNS或IFNS或类型IIFN或类型的反应。两个都。重要的是，鉴定出许多新型的IFN刺激基因在其已知的生物学功能上是多样的。例如，鉴定出几种与凋亡有关的新型ISG（包括Rap46/Bag-1，磷脂cramblase和低氧诱导因子-1alpha）。此外，还鉴定了几个IFN抑制基因。这些结果证明了寡核苷酸阵列在监测较大且前所未有的尺度上监测哺乳动物基因表达中的有用性。特别是，这些发现提供了对IFN作用的基本机制的见解，最终可能有助于更好地治疗IFN的治疗用途。
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.