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dc.contributor.authorH. Wong, Leeen_US
dc.contributor.authorSim, Helenaen_US
dc.contributor.authorChatterjee-Kishore, Moitreyeeen_US
dc.contributor.authorHatzinisiriou, Ireneen_US
dc.contributor.authorJ. Devenish, Rodneyen_US
dc.contributor.authorStark, Georgeen_US
dc.contributor.authorJ. Ralph, Stephenen_US
dc.contributor.editorHerbert Taboren_US
dc.description.abstractThe transcription factor STAT1 plays a pivotal role in signal transduction of type I and II interferons (IFNs). STAT1 activation leads to changes in expression of key regulatory genes encoding caspases and cell cycle inhibitors. Deficient STAT1 expression in human cancer cells and virally mediated inhibition of STAT1 function have been associated with cellular resistance to IFNs and mycobacterial infection in humans. Thus, given the relative importance of STAT1, we isolated and characterized a human STAT1 intronic enhancer region displaying IFN-regulated activity. Functional analyses by transient expression identified a repressor region and type I and II IFN-inducible elements within the STAT1 enhancer sequence. A candidate IRF-E/GAS/IRF-E (IGI) sequence containing GAAANN nucleotide repeats was shown by gel shift assay to bind to IFN regulatory factor-1 (IRF-1), but not to IFN-stimulated gene factor-3 (ISGF-3) or STAT1-3. An additional larger IGI-binding complex containing IRF-1 was identified. Mutation of the GAAANN repeats within the IGI DNA element eliminated IRF-1 binding and the IFN-regulated activity of the STAT1 intronic enhancer region. Transfection of the IFN-resistant MM96 cell line to express increased levels of IRF-1 protein also elevated STAT1, STAT2, and p48/IRF-9 expression and enhanced cellular responsiveness to IFN-. Reciprocating regulation between IRF-1 and STAT1 genes and encoded proteins indicates that an intracellular amplifier circuit exists controlling cellular responsiveness to the IFNs.en_US
dc.publisherThe American Society for Biochemistry and Molecular Biologyen_US
dc.publisher.placeMaryland, USAen_US
dc.relation.ispartofjournalJournal of Biological Chemistryen_US
dc.titleIsolation and characterization of a human STAT1 gene regulatory element: Inducibility by interferon (IFN) types I and II and role of IFN regulatory factor-1en_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.hasfulltextNo Full Text

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