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dc.contributor.authorZaiman, Ari Lev
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 57-08, Section: B, page: 4902.;Advisors: Jack Lenz.
dc.description.abstractDifferential recognition of murine leukemia virus (MuLV) enhancers by cellular transcription factors determines the viral leukemogenic potential. A single base pair difference in an element termed the enhancer core between T-cell lymphomagenic SL3 virus and non-leukemogenic Akv virus significantly affects viral leukemogenicity. One factor that binds the enhancer cores of MuLVs is CBF (AML1). CBF consists of two heterologous subunits both of which have been implicated in human acute myelogenous leukemia. Cotransfection assays were used to investigate the ability of CBF to activate MuLV core elements.;Cotransfection of AML1 with SL3, Akv, or Moloney virus LTR-CAT constructs resulted in a 6-8 fold increase in transcription that depended on the core sites. Two alternatively spliced forms of AML1, that differed at their carboxy termini transactivated the SL3 LTR to different levels. These experiments demonstrated the ability of CBF to transactivate the core, and implicated the C-terminus as an important determinant of transcriptional activity.;Sequences immediately 5{dollar}\sp\prime{dollar} to the SL3 enhancer core bind additional transcription factors including Myb and Ets-1. The ability of AML1 to interact with the adjacent factors was tested. Mutation of the Ets site decreased the ability of AML1 to transactivate the viral core by roughly 50%. Mutation of the Myb site had no effect on the activity of AML1. However, through the use of cotransfections of AML1 and Myb, a functional synergy between AML1 and Myb was detected. This cooperativity occurred even when the Ets site was mutated. Thus, CBF required either Myb or an Ets family member for full activity on the SL3 enhancer. Furthermore, a multimerized reporter consisting of five tandem core binning, sites could not be transactivated by AML1. Thus, AML1 requires other transcription factors to function.;The significance of these elements to the enhancer function in T-cells was then demonstrated by a decreased enhancer activity upon transfection of a series of reporters in which one, two, or three of the sites were mutated. Thus, the cooperativity between the factors demonstrated by the cotransfection experiments can be related to enhancer function in T-cells.
dc.publisherProQuest Dissertations & Theses
dc.subjectMolecular biology.
dc.titleRegulation of the enhancer of a lymphomagenic virus: Characterization of two enhancer core binding proteins

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