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The Specific Role Of The Mll Cxxc Domain In Mll Fusion Protein Function, Laurie Ellen Risner
The Specific Role Of The Mll Cxxc Domain In Mll Fusion Protein Function, Laurie Ellen Risner
Dissertations
The MLL gene was first identified because it is involved in chromosome translocations which produce novel fusion proteins that cause leukemia. The CXXC domain of MLL is a cysteine rich DNA binding domain with specificity for binding unmethylated CpG-containing DNA. The CXXC domain is retained in oncogenic MLL fusions, and is absolutely required for the fusions to cause leukemia. This project explored the role of the CXXC domain by introducing structure-informed point mutations within the MLL CXXC domain that disrupt DNA binding, and by performing domain swap experiments in which different CXXC domains from other proteins, including DNMT1, CGBP and …
Epigenetic Effects Of Benzo(A)Pyrene In Fundulus Heteroclitus And Danio Rerio, Xiefan Fang
Epigenetic Effects Of Benzo(A)Pyrene In Fundulus Heteroclitus And Danio Rerio, Xiefan Fang
Electronic Theses and Dissertations
DNA methylation is one of the epigenetic mechanisms that controls gene expression and is vulnerable to early life environmental toxicant exposures. Our goal was to use two fish models, Fundulus heteroclitus and Danio rerio (zebrafish), to study the benzo(a)pyrene (BaP) effects on DNA methylation status and whether the alterations could contribute to BaP-mediated reproductive and developmental toxicities. Initially, we used Fundulus to study BaP effects on glycine N-methyltransferase (GNMT) expression throughout development. Fundulus embryos were exposed to waterborne BaP at nominally 10 or 100 μg/L and both GNMT mRNA expression and enzyme activity were measured. Quantitative PCR and whole mount …