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Zabierowski, Susan Ellen (2005) DIFFERENTIAL CELLULAR REQUIREMENTS FOR ICP4-MEDIATED ACTIVATION OF HSV-1 EARLY AND LATE GENES. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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The herpes simplex virus type 1 immediate-early protein, ICP4, is the major transcriptional activator of viral early and late genes. ICP4 has been shown to bind DNA and interact with components of the general transcription machinery to activate or repress viral transcription, depending on promoter context. Microarray and northern blot analysis indicated that the abundance of the basal Pol II transcription machinery was significantly altered at late times of infection. Because viral early and late genes have very different promoter architectures, the cellular requirements for ICP4-mediated activation of early and late genes may differ. In testing this hypothesis using tk and gC as representative early and late promoters respectively, the general transcription factor TFIIA was found not to be required for ICP4 activation of the late gC promoter but was essential for activation of the early tk promoter. An intact INR element was required for TFIIA to be dispensable for ICP4 activation of the gC promoter. In the presence of TFIIA, ICP4 overcame the requirement for an intact INR on the gC promoter enhancing ICP4 activation of an INR-mutated gC promoter. When examining the binding properties of TFIIA, ICP4 and TBP/TFIID on early, late, and INR-mutated late promoters, ICP4 could only effectively substitute for TFIIA in stabilizing the binding of TFIID to the TATA box of the late promoter containing a functional INR. ICP4 required the additional activities of TFIIA to stabilize the binding of TFIID to the TATA box of an INR-mutated late promoter. Additionally, microarray and northern blot analysis indicated that TFIIA expression was reduced at late times of infection. The decrease in TFIIA expression during infection, the ability of ICP4 to substitute for TFIIA in stabilizing TFIID binding to an INR-containing late promoter, and its dispensability for activation of late but not early genes suggests a mechanism for the shutoff of early gene expression while allowing the continued expression of late genes.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Zabierowski, Susan Ellensezst5@pitt.eduSEZST5
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDeLuca, Neal Andeluca@pitt.eduNDELUCA
Committee MemberArndt, Karen Aarndt@pitt.eduARNDT
Committee MemberSchmidt, Martin Cmcs2@pitt.eduMCS2
Committee MemberKhan, Saleem Akhan@mgb.pitt.eduKHAN
Committee MemberSmithgall, Thomas Etsmithga@pitt.eduTSMITHGA
Date: 28 April 2005
Date Type: Completion
Defense Date: 22 April 2005
Approval Date: 28 April 2005
Submission Date: 28 April 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Molecular Virology and Microbiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: HSV-1; ICP4; transcription; transcription factors; viral gene expression
Other ID:, etd-04282005-105122
Date Deposited: 10 Nov 2011 19:42
Last Modified: 15 Nov 2016 13:42


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