Characterization of the promoter of the human gene encoding the high-affinity IgG receptor: transcriptional induction by gamma-interferon is mediated through common DNA response elements.

Abstract

(IFN-a/f3) and type II (IFN-y). Both act through typespecific cell surface receptors to induce the expression of unique, although overlapping, sets of genes. Genes that are induced only by IFN-a/13, such as ISG15 and ISG54, or by both IFN-a/fB and IFN-y, such as the guanylate-binding protein (GBP) and major histocompatibility (MHC) class I genes, appear to share a common mechanism for transcriptional regulation, which is mediated by a conserved sequence, termed the IFN-stimulated response element (ISRE) (2-6). Interaction of IFN-a/p with its receptor activates a positive regulatory factor, ISGF3, that binds to the ISRE (7). IFN-y can enhance this effect by stimulating the synthesis of the DNA-binding subunit ofISGF3 (8). An additional element overlapping the ISRE has been identified in the GBP promoter (4, 9). Termed the gamma-activated sequence (GAS), this element contributes to both IFN-a//3 and IFN-y transcriptional activation by binding distinct trans-acting factors. In contrast, a common mechanism of transcriptional induction has yet to be established for genes that are responsive to IFN-y but not to IFN-a/f3. Included in this set are genes encoding IP-10, monokine induced by IFN-y (MIG), macrophage inhibitory protein 2, MHC class II antigens, the MHC class II-associated invariant chain, and the highaffinity receptor for IgG (Fc,, receptor type I, FcXRI) (10-15).Among the cis-acting elements shown to mediate the IFN-y activation of these genes are the ISRE of the invariant-chain gene promoter and the X, H, and y-IRE sequences of MHC class II gene promoters (16)(17)(18)(19)(20)(21). We are interested in determining the mechanisms by which IFN-y is able to regulate the immune response, and have focused our work on the DNA elements responsible for the transcriptional induction of the human FcXRI gene. In this paper we present the structure of the gene encoding human FcXRI (huFcRI),t focusing on the structure of its promoter and characterization of the DNA sequences responsible for its induction by IFN-y. A 39-base-pair (bp) cis-acting region, termed the IFN-y response region (GRR), is shown to be responsible for IFN-y induction and to be sufficient to confer pronounced IFN-y inducibility upon a heterologous promoter. The GRR contains elements homologous to those defined for MHC class II promoters and several other IFN--responsive genes, indicating that, as in the case of IFN-a/f3-responsive genes, common sequence motifs are involved in transcriptional activation of this class of genes.

Alteration in the gene expression pattern of primary monocytes after adhesion to endothelial cells

“…Thus, adhesion to the endothelium does not only regulate genes that are required for subsequent transendothelial migration but might also initiate the differentiation program of monocytes. This would be in agreement with the finding that HUVEC-attached monocytes showed an up-regulation of CD74 (35), caveolin-1 (36,37), and CD64 (40). CD74 (invariant chain) is required for antigen presentation on major histocompatibility complex class II molecules (35).…”

“…Caveolin-1 and caveolin-2 have been identified as providing a novel route by which several pathogens are internalized by antigen-presenting cells (36,37). CD64 (Fc-␥-RI) is constitutively expressed on monocytes and represents a high-affinity Fc-␥ receptor that plays a pivotal role in the immune response (40). A schematic overview is given in Fig.…”

Interferonγ Activation of Raf-1 Is Jak1-dependent and p21ras-independent

“…1A) as measured by the inability of IFN␥ to activate STAT1-dependent DNA binding to a GAS-like element referred to as the GRR, which is located in the promoter of the high affinity Fc␥ receptor I gene (15) (Fig. 1A, lanes 6 -10).…”

“…DNA-binding proteins were assayed as described previously (14). Briefly, 10 g of protein were incubated in binding buffer with the 32 P-labeled oligonucleotide probe consisting of the double-stranded IFN␥ activation sequence (GAS) referred to as the gamma response region (GRR) (5Ј-AGCATGTTTCAAGGATTTGAGAT-GTATTTCCCAGAAAAG-3Ј) of the promoter of the Fcgr1 gene (15). The sample was then applied to a 6% nondenaturing polyacrylamide gel to separate free probe from probe bound to protein.…”

Positive Selection of Apoptosis-resistant Cells Correlates with Activation of Dominant-Negative STAT5

“…To obtain whole cell extracts (WCE), cells were resuspended in a high salt buffer (20 mM Hepes, pH 7.9, 0.4 M NaCl, 1 mM EDTA, 1 mM EGTA, 1 mM dithiothreitol supplemented with 1 mM Na 3 V0 4 , 50 mM NaF and a standard protease inhibitors mixture) and lysed by three freeze-thaw cycles in liquid N 2 . Electrophoretic mobility shift assays (EMSAs) were performed as described previously (36) using as a probe an oligonucleotide corresponding to the IFN-␥-responsive region (GRR) located within the promoter of Fc␥RI gene (37).…”