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AP-1-MEDIATED REGULATION OF HPV CHROMATIN TRANSCRIPTION

Wang, Wei-Ming
http://rave.ohiolink.edu/etdc/view?acc_num=case1199480473

Abstract Details

2008, Doctor of Philosophy, Case Western Reserve University, Biochemistry.
AP-1 complexes are a family of transcription factors ubiquitously expressed in different cell types. Transcriptional regulation mediated by AP-1 has been extensively studied; AP-1 mainly works through its cognate sequences, which are found in the regulatory elements in a variety of genes. Current genome-wide promoter occupancy studies indicate that the regulatory specificity is conferred mainly through combinatorial transcription factor binding elements containing non-consensus low affinity sites. However, the question of whether the binding sequences possess intrinsic selectivity for a given family transcription factors, which exhibit overlapping binding preference, is hard to define in living cells. Our in vitro biochemical studies unambiguously demonstrated that distinct AP-1 sites, derived from the HPV-11 upstream regulatory region (URR), indeed exhibit differential binding properties toward distinct recombinant human AP-1 complexes. Importantly, we further disclosed a conserved consensus-like binding site existing near the E6 core promoter across different genital HPVs based on an in-depth analysis of our in vitro experimental data. It is noteworthy that the investigation of AP-1-mediated regulation of HPV chromatin transcription is significantly facilitated by the strategy of in vivo reconstitution of coexpressed human AP-1 subunits using a polycistronic bacterial expression system to generate various full-length recombinant AP-1 complexes, which were applied to various in vitro functional assays performed in the present work. Previously we found that both AP-1 and p300 are required for activation of HPV chromatin transcription; however, the underlying mechanism remains unclear. We demonstrated that AP-1 recruits p300 to stimulate in vitro HPV chromatin transcription mainly depends on acetylation of nucleosomal histones by p300. Interestingly, p300 can also mediate acetylation of all the subunits of AP-1 complexes, whose DNA binding activity is stimulated by acetylation. Interestingly, we addressed the molecular mechanism and the functional role of p300-mediated acetylation on AP-1 transcription factors. Furthermore, the finding of targeted histone acetylation surrounding the redundantly occupied HPV E6 promoter-proximal AP-1 site demonstrated in living cells implicates a biologically important role played by AP-1 and possibly uncovers a common mechanism underlying the HPV pathogenesis.
Cheng-Ming Chiang (Advisor)
AP-1; p300; HPV; chromatin; transcription; Jun; Fos

Recommended Citations

Citations

  • Wang, W.-M. (2008). AP-1-MEDIATED REGULATION OF HPV CHROMATIN TRANSCRIPTION [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1199480473

    APA Style (7th edition)

  • Wang, Wei-Ming. AP-1-MEDIATED REGULATION OF HPV CHROMATIN TRANSCRIPTION. 2008. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1199480473.

    MLA Style (8th edition)

  • Wang, Wei-Ming. "AP-1-MEDIATED REGULATION OF HPV CHROMATIN TRANSCRIPTION." Doctoral dissertation, Case Western Reserve University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1199480473

    Chicago Manual of Style (17th edition)

case1199480473
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© 2008, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.