alpha-Interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences

Abstract

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 recently, and by interferon regulation of transcription has been demonstrated for several of the eight mRNAs, with a significant increase apparent in as little as 5 min. We now show that IFN-alpha treatment results in a three- to fivefold increase in the transcription of MT2 and HLA class I genes in human T98G neuroblastoma cells. Furthermore, comparison of regions upstream of the MT2A gene, two HLA genes and one HLA class II gene reveals a homologous sequence of approximately 30 base pairs (bp) which may be involved in regulating transcription of interferon-induced genes. Transcription of the mRNA for human MT2A is induced by glucocorticoids or metal ions and the regulatory elements have been mapped by promoter-fusion experiments. We now show that the rate of transcription of MT2A is 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.