ALPHA-INTERFERON-INDUCED TRANSCRIPTION OF HLA AND METALLOTHIONEIN GENES CONTAINING HOMOLOGOUS UPSTREAM SEQUENCES
ALPHA-INTERFERON-INDUCED TRANSCRIPTION OF HLA AND METALLOTHIONEIN GENES CONTAINING HOMOLOGOUS UPSTREAM SEQUENCES
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DOI：
10.1038/314637a0
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发表时间：
1985-01-01
期刊：
影响因子：
64.8
通讯作者：
STARK, GR
中科院分区：
文献类型：
--
作者：
FRIEDMAN, RL;STARK, GR
与干扰素（IFN）诱导的组织相容性位点抗原（HLA）、金属硫蛋白-II（MT 2）、2′，5 ′-寡腺苷酸合成酶和大约8种其他未知序列蛋白质的信使RNA相对应的互补DNA最近已被分离1 -5，并且已证实8种mRNA中的几种mRNA转录受干扰素调节3，4，在短短5分钟内明显增加。我们现在发现IFN-α处理导致人T98 G神经母细胞瘤细胞中MT 2和HLA I类基因转录增加3 - 5倍。此外，通过比较MT 2A基因、两个HLA基因和一个HLA II类基因的上游区域，发现了一个约30 bp的同源序列，该序列可能参与了干扰素诱导基因的转录调控。人类MT 2A的mRNA转录是由糖皮质激素或金属离子诱导的6，7，并且调控元件已经通过启动子融合实验绘制了图谱8。我们现在发现，在用干扰素或地塞米松治疗时，MT 2A的转录速率是相同的，但是用地塞米松治疗时，mRNA的积累要快得多，这表明转录后事件在后一种情况下是重要的。
Complementary DNAs corresponding to the Interferon (IFN)-induced messenger RNAs for histocompatibility locus antigens (HLA), metallothionein-II (MT2), 2′,5′-oligoadenylate synthetase and about eight other proteins of unknown sequence have been isolated recently1–5, and by interferon regulation of transcription has been demonstrated for several of the eight mRNAs3,4, with a significant increase apparent in as little as 5 min3. We now show that IFN-αtreatment results in a three- to fivefold increase in the transcription ofMT2andHLAclass I genes in human T98G neuroblastoma cells. Furthermore, comparison of regions upstream of theMT2Agene, twoHLAgenes and oneHLAclass II gene reveals a homologous sequence of ∼30 base pairs (bp) which may be involved in regulating transcription of interf eron-induced genes. Transcription of the mRNA for humanMT2Ais induced by glucocorticoids or metal ions6,7and the regulatory elements have been mapped by promoter-fusion experiments8. We now show that the rate of transcription ofMT2Ais the same on treatment with interferon or dexamethasone, but that the mRNA accumulates much faster with dexamethasone, indicating that post-transcriptional events are important in the latter case.