Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


Final Rakijas Dissertation.pdf (2.21 MB)

ETD Abstract Container

Abstract Header

E2Fs and Transcription: New Members Help Answer Old Questions

Rakijas, Jessica B
http://rave.ohiolink.edu/etdc/view?acc_num=osu1492780032915208

Abstract Details

2017, Doctor of Philosophy, Ohio State University, Molecular Genetics.
The Rb-E2F pathway is a critical signaling axis that controls cell cycle transitions. The E2F family of transcription factors comes in two varieties: activators (E2F1-3) and repressors (E2F4-8). The Rb tumor suppressor can repress E2F target gene expression through physical interaction with both E2F1-3 activators and E2F4-6. The non-canonical E2F7-8 members repress gene expression independent of interaction with Rb. , Site-specific transcription factors, such as E2F, are believed to require their consensus DNA binding sequence in order to assert their function. However, it is unclear how E2F family members can both activate and repress the same genes through the same DNA binding site. Thus, the purpose of this study is to test the assertion that all E2Fs require the presence of an intact DNA binding site to regulate target gene expression in a periodic fashion during the cell cycle, development, and cancer. We have taken multiple approaches to investigate the requirement of E2F-binding sites for transcriptional regulation of genes in both mouse embryo fibroblasts (MEFs) and intact mouse tissues. We generated a novel N-terminal 5x-myc tagged E2F8 knock-in mouse with a two amino acid substitution that is sufficient to abrogate DNA binding. In vivo analyses of this mouse have shown that the DNA binding ability of E2F8 is required during development and, endoreduplication, as well as for the suppression of hepatocellular carcinoma (HCC). In a parallel effort, we generated several novel knock-in mouse of critical cell cycle genes, Cyclin A2 (Ccna2) and Cell division cycle-6 (Cdc6) wherein mutations disrupting the well-established E2F binding sites introduced into each gene promoter. This study concludes that the E2F binding sites in the Ccna2 and Cdc6 promoters are required for cell cycle and developmental oscillatory expression of Ccna2 and Cdc6 transcription.
Susan Cole, PhD (Advisor)
Gustavo Leone, PhD (Advisor)
Christin Burd, PhD (Committee Member)
Dawn Chandler, PhD (Committee Member)
138 p.
Biochemistry; Biology; Genetics
Cell cycle, E2F, Cdc6, Ccna2, Mouse model

Recommended Citations

Citations

  • Rakijas, J. B. (2017). E2Fs and Transcription: New Members Help Answer Old Questions [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492780032915208

    APA Style (7th edition)

  • Rakijas, Jessica. E2Fs and Transcription: New Members Help Answer Old Questions. 2017. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1492780032915208.

    MLA Style (8th edition)

  • Rakijas, Jessica. "E2Fs and Transcription: New Members Help Answer Old Questions." Doctoral dissertation, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492780032915208

    Chicago Manual of Style (17th edition)

osu1492780032915208
143
© 2017, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.