One of the main goals of this project was to systematically evaluate the virus-inducible properties of the individual human interferon-beta (IFN-$ beta$) enhansons. Synthetic oligonucleotides representing the different enhansons were subcloned into an enhancerless SV$ sb1$CAT vector; the hybrid plasmids obtained were tested in different human cell lines by transient expression assay. The P2 motif, which is 80% homologous to the NF-$ kappa$B recognition sequence, was inducible by Sendai virus. In contrast, the P1 enhanson was transcriptionally silent. Unexpectedly, a multimer of the P5 motif conferred significant virus inducibility to a heterologous transcription unit. A DNA fragment encompassing P5, P1, and P2 mimicked the transcriptional activity of the whole IFN-$ beta$ promoter, indicating that the three enhansons act synergistically to confer a virus-inducible expression pattern. The effect of certain trans-acting factors on the individual IFN-$ beta$ enhansons was also assessed. Together, these experiments indicate that the synergism between the P5, P1, and P2 enhansons is mediated by at least two distinct transcription factors, NF-$ kappa$B and IRF-1.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.59923 |
| Date | January 1990 |
| Creators | Leblanc, Jean-François |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Microbiology and Immunology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001213498, proquestno: AAIMM67487, Theses scanned by UMI/ProQuest. |
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