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Identifying novel genes involved in zinc homeostasis using a fission yeast model

Liu, Yi-Hsuan

Abstract Details

2015, Master of Science, Ohio State University, Human Ecology: Human Nutrition.
Metals, such as iron, zinc, copper, and manganese are needed to maintain normal biological and cellular functions and are therefore essential for all organisms. Zinc plays a particularly important role in biological systems as it is a cofactor for many different proteins. However, in excess, zinc is toxic to cell growth. As a consequence, mechanisms to regulate the import, export, and availability of zinc are found in all living organisms to maintain optimal zinc levels. Although zinc is essential for life, knowledge of how zinc homeostasis is regulated at the transcriptional, post-transcriptional, translational, and post-translational level is relatively limited. In humans, aberrant zinc levels are observed in a large number of disorders, such as acrodermatitis enteropathica and pancreatic cancer (Neldner and Hambidge 1975, Li et al. 2007). Therefore, identifying factors that affect zinc homeostasis is important to understand the connections that exist between zinc and disease. In the fission yeast Schizosaccharomyces pombe, a protein called Loz1 (for Loss Of Zinc sensing 1) plays an important role in the transcriptional regulation of genes involved in zinc homeostasis and zinc-dependent cellular pathways. Loz1 is a transcriptional factor that represses target gene expression under zinc-replete conditions. Cells that lack Loz1 constitutively express genes required for zinc uptake and therefore hyperaccumulate zinc. Using this characteristic, I utilized Loz1 as a tool to study mechanisms of zinc homeostasis, and identify additional factors involved in zinc-dependent processes. Genes that Loz1 regulates includes zrt1 and zym1, which encodes a high affinity zinc uptake system and zinc binding metallothionein, respectively (Dainty et al. 2008, Borrelly et al. 2002). As Loz1 regulates the expression of genes critical to zinc homeostasis, I hypothesized that other Loz1 target genes may also play an important role in zinc homeostasis. In this thesis, I use RNA-seq analysis to identify new Loz1 targets. In addition, as cells lacking Loz1 hyperaccumulate zinc, I take advantage of this phenotype to identify genes involved in mitochondrial zinc transport.
Amanda Bird (Advisor)
Earl Harrison (Committee Member)
Kichoon Lee (Committee Member)
103 p.

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Citations

  • Liu, Y.-H. (2015). Identifying novel genes involved in zinc homeostasis using a fission yeast model [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1428660969

    APA Style (7th edition)

  • Liu, Yi-Hsuan. Identifying novel genes involved in zinc homeostasis using a fission yeast model. 2015. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1428660969.

    MLA Style (8th edition)

  • Liu, Yi-Hsuan. "Identifying novel genes involved in zinc homeostasis using a fission yeast model." Master's thesis, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1428660969

    Chicago Manual of Style (17th edition)