Regulation of Gene Expression by Interferons: Control of H-2 Promoter Responses

Korber, Bette; Mermod, Nicolas; Hood, Leroy; Stroynowski, Iwona

doi:10.1126/science.3125612

Cited by 131 publications

(78 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These observations raised the question of whether sequences other than the 5Ј-flanking region of the HLA-A2 gene could be necessary for IFN-␥ induction. In this regard, studies in both the mouse H-2L gene and the human HLA-B7 gene have shown that sequences located 3Ј to the transcription initiation site are both necessary for full response to IFN-␥ and sufficient to mediate some IFN-␥ response (17,18,21). Our results show that in K562 cells, which had been stably transfected with an HLA-A2 genomic clone containing 525 bp of the 5Ј promoter, all eight exons, and ϳ1300 bp of 3Ј-transcribed region, IFN-␥ stimulation increases the level of RNA from the transfected gene by 3-fold.…”

Section: Discussionmentioning

confidence: 99%

“…Other class I genes, such as HLA-B7 and the murine H-2L and H-2K genes, have been shown to have a functional ISRE region which, by itself, can mediate a strong transcriptional response to IFN-␥ most likely involving the Janus kinase (Jak)/Stat family of protein kinases (18,57). In addition, transcription of the class Ib gene HLA-E has been shown to be stimulated by IFN-␥ through a unique IFN response element, the interferon response region, through the Jak/Stat pathway (58).…”

Section: Discussionmentioning

confidence: 99%

“…IFN-␥ induction of many class I genes is mediated, at least in part, by the ISRE located within the 5Ј promoter of the gene (17,18,35). CAT expression constructs consisting of 525 bp of the HLA-A2 promoter, either containing or lacking the ISRE, were transiently transfected into both K562 and Jurkat cells to determine whether IFN-␥ up-regulates expression of the HLA-A2 gene through the ISRE.…”

Section: A Transfected Full-length Hla-a2 Gene Is Inducible With Ifn-␥mentioning

confidence: 99%

“…Studies of the mouse H-2L gene have shown that while the ISRE was necessary for full IFN induction, the H-2L mRNA was still up-regulated 2-to 4-fold by IFN-␥ when the entire 5Ј promoter of the gene was replaced with a feline leukemia virus promoter (17)(18)(19). A similar result was obtained in the human HLA-B7 gene, in that a truncated HLA-B7 gene lacking the 5Ј promoter region was IFN-inducible when transfected into mouse L cells (20).…”

mentioning

confidence: 99%

See 3 more Smart Citations

A 3′-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-γ

Snyder

Waring

Sheng

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

The expression of several MHC class I genes is up-regulated at the transcriptional level by IFN-γ. Posttranscriptional mechanisms also have been implicated, but not well characterized. To investigate the mechanism of IFN-γ stimulation of the human MHC class I gene HLA-A2, several human tumor cell lines were transfected with reporter gene constructs driven by the HLA-A2 promoter. We have previously shown that the extended 525-bp HLA-A2 promoter alone, which includes a 5′ IFN-stimulated response element consensus sequence, is not sufficient for IFN-γ response in either K562 or Jurkat cells. In the current study, stable transfection of a genomic HLA-A2 gene construct, containing both 5′- and 3′-flanking sequences, resulted in stimulation of the gene by IFN-γ. Nuclear run-on assays revealed that, unlike other class I genes, IFN-γ stimulation of HLA-A mRNA accumulation occurs almost entirely through posttranscriptional mechanisms. RNA stability assays showed that the effect is not mediated by alteration of the half-life of the HLA-A2 mRNA. Formation of the 3′ end was unaffected by IFN-γ treatment. Sequences that mediate the majority of IFN-γ induction of HLA-A2 mRNA reside in a 127-bp 3′-transcribed region of the gene. This region contains the terminal splice site, the usage of which is not affected by IFN-γ treatment. These results demonstrate a novel posttranscriptional mechanism of regulation of MHC class I genes by IFN-γ.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: A Transfected Full-length Hla-a2 Gene Is Inducible With Ifn-␥mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

A 3′-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-γ

Snyder

Waring

Sheng

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The cytokines IFN-gamma and TNF-alpha produced during the immune response have been shown to inhibit transgene expression from viral promoters. [10][11][12][13] In addition, cytotoxic T lymphocytes (CTL) and neutralizing antibodies are also likely to be involved in limiting the persistence of transgene expression. In certain situations it would be highly desirable to readminister the gene of interest.…”

Section: Introductionmentioning

confidence: 99%

Variation in the immune response to adenoviral vectors in the brain: influence of mouse strain, environmental conditions and priming

et al. 1999

View full text Add to dashboard Cite

E1-deleted adenoviral vectors expressing the bacterial ␤-ently made higher antibody responses than C57BL/6J galactosidase gene were inoculated into the brain of mice. Although adenoviral vectors induced an inflammatory unprimed and primed C3H.He or C57BL/6J mice housed response under all conditions, mice housed in SPF faciliunder either conventional or specific-pathogen-free (SPF) ties exhibited less inflammation than conventional mice conditions. The kinetics of immune responses to both the and transgene expression persisted for longer. Irrespective vector and the transgene were investigated. In mice preof whether the mice had been deliberately primed to adenviously sensitized to adenovirus, the leukocyte infiltrate in ovirus, antibody titres were consistently lower in SPF mice the brain was dominated by CD8 + T cells, whereas in compared with conventional mice. This study clearly demunprimed mice CD4 + T cells were present at higher levels.onstrates that environmental conditions, as well as preAs expected, antibody titres to both adenovirus and ␤-vious priming to adenovirus, will affect both the quality and galactosidase were higher in primed mice than in unprimed duration of the immune response triggered by gene mice after intracranial inoculation. C3H.He mice consistdelivery to the brain.

show abstract

Antibodies to HLA class I promoter‐binding proteins in sera from patients with systemic lupus erythematosus

Bouteiller¹,

Auphan²,

Weill³

et al. 1989

Eur J Immunol

View full text Add to dashboard Cite

Antibodies directed against human cell nuclear factors (HLA-F1 and HLA-F2) that bind to the interferon consensus sequence (ICS) in the promoter region of the HLA-A2 class I gene can be detected in the serum of some patients with systemic lupus erythematosus (SLE). Such antibodies, in gel-shift assays, inhibited the formation of the retarded band corresponding to the HLA-F1/F2-ICS complex irrespective whether purified factors or crude nuclear extracts were used. This inhibitory effect was due to IgG since the SLE serum activity bound to and could be eluted from a protein A-Sepharose column. This effect still persisted after absorption of SLE serum on a DNA-affinity column which removed antibodies directed against protein-free HLA-A2-ICS nucleotide sequence also present in such sera. Western blot analysis further confirmed that SLE serum recognized both HLA-F1 (65 kDa) and HLA-F2 (88 kDa) polypeptides, independently of the presence of the HLA-A2-ICS nucleotidic sequence, as well as other proteins. These results suggest that human sera from some patients with SLE may be used as a convenient source of antibodies directed against DNA-binding proteins regulating gene transcription.

show abstract

Regulation of Gene Expression by Interferons: Control of H-2 Promoter Responses

Cited by 131 publications

References 40 publications

A 3′-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-γ

A 3′-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-γ

Variation in the immune response to adenoviral vectors in the brain: influence of mouse strain, environmental conditions and priming

Antibodies to HLA class I promoter‐binding proteins in sera from patients with systemic lupus erythematosus

Contact Info

Product

Resources

About