The interferon (IFN)-activated human 2',5'-oligo(A) synthetase E gene contains 11 RNA starts and lacks TATA and CAAT signals. DNA sequences around the promoter make the expression of the chloramphenicol acetyltransferase gene (CAT) inducible over 20-fold by IFN. A 72-base-pair segment (E-IRS) immediately upstream of the RNA starts was defined as being required for IFN-activated expression of the E-gene promoter-CAT constructs and acts in a position-independent manner. It also confers IFN-activated enhancement to the herpes simplex virus thymidine kinase promoter. On this promoter, the 5' part of the E-IRS functions as a constitutive enhancer, while the last 16 base pairs of the E-IRS is sufficient to give IFN-induced expression. On the E-gene promoter, the constitutive enhancer and the IFN-activated sequence are both needed but can be separated. In addition, promoter competition experiments indicate a third regulatory region which helps to repress expression of the E gene in uninduced cells.

The human high-affinity receptor for the constant region of immunoglobulin G (human Fc'yRl)

Treatment of responsive cells by interferons (IFNs) induces within a few hours a rise in the concentration of several proteins and mRNAs. In order to characterize these IFN-induced mRNA species, we have cloned in E. coli the cDNA made from a 17-18S poly(A)+ RNA of human fibroblastoid cells (SV80) treated with IFN-beta. We describe here a pBR322 recombinant plasmid (C56) which contains a 400 bp cDNA insert corresponding to a 18S mRNA species newly induced by IFN. The C56 mRNA codes for a 56,000 dalton protein easily detectable by hybridization-translation experiments. The sequence of 66 of the carboxy-terminal amino-acids of the protein can be deduced from the cDNA sequence. IFNs-alpha, beta or gamma are able to activate the expression of this gene in human fibroblasts as well as lymphoblastoid cells. The mRNA is not detectable without IFN; it reaches maximum levels (0.1% of the total poly(A)+ RNA) within 4-8 hrs and decreases after 16 hrs.

Induction by gamma interferon (IFN-,y) of the gene encoding the human high-affinity Fcy receptor (FcyRl) in myeloid cells requires an IFN--y response region (GRR) and a myeloid cell-activating transcription element (MATE). GRR and MATE interact with factors to form, respectively, an IFN--y-activating complex (GIRE-BP), depending on the phosphorylation of the 91-kDa protein (subunit of ISGF3), and a cell-type-specific complex (MATE-BP Our approach to characterization of lineage-specific transcription factors was to study the mechanisms of expression of a lineage-specific marker gene such as the gamma interferon (IFN--y)-induced gene encoding the human high-affinity receptor for immunoglobulin G (Fc-yRl) (1). Studies of its promoter led to the identification of two cis-DNA elements, IFN-y responsive region (GRR) (2, 28) and myeloid cell-activating transcription element (MATE) (31), involved, respectively, in its IFN-y-induced and myeloid cell-restricted expression.The GRR motif is a target for proteins forming an IFN-oa-or IFN--y-activated complex, 31,49). At least, one IFN regulatory factor, the 91-kDa protein (7,17,21), was identified as a component of 29,31). Tyrosine phosphorylation of this factor and of two other factors of 113 and 84 kDa (37) depends on the activation of Tyk2 (46) and JAK1 (23) following binding of IFN-at to its cell surface receptor. After translocation to the nucleus (17), these factors are found to be associated with a 48-kDa DNA-binding protein (21) targeting the IFN-stimulated response element (ISRE) to form a complex referred to as ISGF3 (7). Although GIRE-BP