α-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^1–5, and by interferon regulation of transcription has been demonstrated for several of the eight mRNAs^3,4, with a significant increase apparent in as little as 5 min³. We now show that IFN-^α 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 ∼30 base pairs (bp) which may be involved in regulating transcription of interf eron-induced genes. Transcription of the mRNA for human MT2A is induced by glucocorticoids or metal ions^6,7 and the regulatory elements have been mapped by promoter-fusion experiments⁸. 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.