Studying the Roles of Posttranslational Histone Modifications in Gene Regulation (2012)

Undergraduates: Sarah Anderson, Lauren Wooten, Robert Williams Mike Meers Pamela Malek, Dr. Greg Matera

Faculty Advisor: Robert Duronio
Department: Biology

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Proper gene regulation is essential to the well-being of organisms, allowing for cell diversification in different types of tissues during development, and for maintenance of cell identity. Defects in gene regulation are an underlying cause to many diseases, and are thought to be particularly important in the onset of cancer. However, more research is needed into the modes of gene regulation and how they function. My research focuses on a probable avenue of gene regulation: post-translational modifications (PTMs) of histones. Histones are organizational proteins that help package DNA within a cell. Histone proteins are also post-translationally modified by the addition of different chemical groups to the N terminal tail. While these modifications are thought to affect the expression of genes, their role has never been directly studied in higher eukaryotes. My project aims to create lines of Drosophila melanogaster with mutant histone proteins that cannot be modified at certain sites. This will be done by replacing the wild type histone locus, which contains 23 tandem repeats of the 5 histone genes, with a mutant locus containing 12 repeats of the 5 histone genes. Currently I am working to create 12 copy repeats of several histone mutants within a Bacterial Artificial Chromosome (BAC). I have so far succeeded in creating 8 different mutations within the histone gene, and I have been successful in obtaining 4 copies of at least one mutant within a BAC.