Date Thesis Awarded
Bachelors of Science (BS)
Altered gene expression is a hallmark of neurodegenerative disorders such as Huntington’s disease. The causative agent of Huntington’s is a mutant, aggregation-prone fragment of huntingtin (htt) that aggregates in the cytosol and nuclei of neuronal cells. The severity and onset of Huntington’s is correlated with the length of a polyglutamine (Q) tract encoded in the N-terminus of htt. Little is known about the nuclear accumulation of polyQ expanded htt, how it interacts with chromatin, and dysregulates transcriptional activity. In this thesis, we investigate the effect of nuclear localized htt on reporter gene activation and demonstrate that the human SUMO-targeted ubiquitin ligase RNF4 reduces htt’s transcriptional activity in a tissue culture model of Huntington’s disease. Additionally, we tested the capacity of RNF4 truncations to modulate htt expression – RING and SIM deletions of RNF4 were found to have enhanced inhibitory function compared to full length RNF4, and these unexpected findings are discussed. In summary, our results provide novel insights into the nuclear functions of htt and suggest a model for the functional interaction with SUMO-targeted ubiquitin ligases.
Peek, Jen, "The Role of RNF4 in Stripping Transcriptionally-Active Huntingtin" (2017). Undergraduate Honors Theses. Paper 1145.