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A Mutagenic Screen Identifies Jim as a Regulator of Transposition, Heterochromatin, and Aging


Transposable elements (TEs) are potentially harmful DNA sequences that can copy themselves and then insert elsewhere into the genome, causing damage and disrupting normal gene function. Research from our lab and others indicates that TEs become highly activated with advanced age, and that hyper-activity of TEs is associated with shorter lifespan. Most TEs are normally confined in heterochromatin, tightly-bound areas of the genome that are transcriptionally repressed. However, one theory of aging posits that epigenetic changes lead to the loosening of heterochromatin over time, thus allowing the expression of deleterious sequences such as TEs. To identify new genes which may help silence TEs, we performed a screen by inducing random mutations into a population of flies, and screening for flies with greatly increased activation of TEs. Through this screen, we identified the zinc finger transcription factor jim as a potential TE regulator. Previous studies have proposed that jim is a heterochromatin enhancer; thus, we decided to study jim in greater depth to determine its role in TE regulation and to elucidate its function at the cellular and organismal levels. We found that loss of jim leads to increased TE expression, and that jim overexpression can block age-related TE increases. Too much overexpression, however, can result in developmental lethality or drastically shortened lifespan. We also found increased levels of the heterochromatin marker H3K9me2 in flies overexpressing jim, thus supporting previous findings that jim enhances heterochromatin. Our results provide promising support for the hypothesis that jim can regulate TE expression via heterochromatin-induced silencing, and therefore affect lifespan and the aging process as a whole.
Senior thesis (ScB)--Brown University, 2020
Concentration: Applied Math - Biology

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Liu, Julianna J., "A Mutagenic Screen Identifies Jim as a Regulator of Transposition, Heterochromatin, and Aging" (2020). Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations. Brown Digital Repository. Brown University Library.