Proposal 0744814 Epigenetic Regulation by Eggless, a Histone Methyltransferase, in Oogenesis and Development.
Although genes are often thought of as simple sequences of DNA that are passed from one individual to another, modification of the DNA and of the proteins that associate with it (epigenetic modifications) can affect gene function profoundly. One such modification, the methylation of histone proteins (the proteins that organize the DNA), is carried out by enzymes called Histone Methyltransferases (HMTs). While the biochemistry of HMT activity has been well-characterized, the biological roles of these enzymes are largely unknown. Previous research in the Hazelrigg lab showed that Eggless (Egg), the fly homolog of a specific human HMT, is required for normal development and for oogenesis, and recent experiments suggest that Egg may be required for germ stem cell maintenance in adult flies. Genetic and molecular tools will be used to determine the roles played by Egg during development and oogenesis. Genetic experiments will determine the developmental consequences of the complete loss of Egg activity, the contributions played by various parts of the Egg protein, and the localization patterns of Egg in particular cells during oogenesis. One particularly interesting challenge is determining which cells (the stem cells or the associated cells) need Egg for normal stem cell maintenance. This proposal has many Broader Impacts. First, since certain cancers have altered patterns of histone methylation, understanding the normal role of histone methylation should provide insights into how aberrant histone methylation contributes to the development of cancer. Second, learning how Egg contributes to stem cell maintenance should have Broader Impacts for the study of adult stem cells with critical implications for medicine due to the potential of stem cell therapies. Finally, the proposed research will provide educational opportunities not only for graduate students and postdocs, but also for undergraduate students who work on independent research projects as part of their education.
