Huntington’s disease (HD) is a progressive and fatal neurodegenerative disorder whose pathogenic mechanism is still not entirely understood. However, previous studies have indicated the prevalence of transcriptional dysregulation in the presence of mutant huntingtin (mHtt). For example, DNA methylation of the promoter region, a mechanism that represses transcription, has been observed to be abnormal in the presence of mHtt. Furthermore, a previous study conducted in 2016 by Pan et al. showed rehabilitating effects against mHtt induced toxicity by the inhibition and knockdown of certain DNA methyltransferase enzymes (DNMTs), DNMT1 and DNMT3A, which catalyze DNA methylation. DNMT3A forms a multi protein complex; the current study hypothesizes that certain differences within this complex between wild type (WT) and mHtt expressing neurons is responsible for the abnormal recruitment of DNMT3A to certain loci in the HD context and is, therefore, causing repression of certain genes essential to neuronal health. To validate this, co immunoprecipitation of DNMT3A within WT and HD models followed by mass spectrometry will be performed to then note any differences in the identified proteins. If this hypothesis is supported by the results of this study, a greater understanding of the pathogenesis of HD will be attained as well as an increased potential of identifying a therapeutic solution for HD.

Fatima Al-Hanoosh would like to thank the McNair staff for their nomination and for providing the great opportunity that is the McNair Summer Research Internship Program, which allowed Fatima to not only begin this project but grow as a researcher too. She is also grateful for their support and constant encouragement throughout this research endeavor. Fatima would like to thank Dr. Hiroko Yano as well for her extensive guidance in this research project. Dr. Yano welcomed Fatima into her lab almost two years ago and has worked tirelessly with her since to achieve the success of this project. Thank you!"