Epigenetic Silencing of Gene Expression in Saccharomyces Cerevisiae

Wesleyan University, Middletown CT

Investigators

Abstract

Intellectual Merit: Genetic differences in DNA sequence between two individuals can be manifested as differences in the individual's physical characteristics and functions. The term epigenetics refers to the fact that two organisms, or two cells within the same organism, can have identical genetic information (the same DNA sequence) but have very different characteristics and functions. Epigenetic controls are essential in establishing the hundreds of distinct cell types (e.g., skin, muscle, liver) in complex organisms such as humans. Cells within an organism have the same DNA, and therefore identical genes, but can assume unique morphologies and functions by establishing unique patterns of gene expression, expressing some genes while turning others off. The DNA in cells is organized into structures known as chromosomes. A key mechanism for controlling whether genes are on or off is by altering the structure of the chromosome. Once established, these alterations can become a stable, heritable part of the chromosome. The nature of these structures and the manner in which they are inherited is not clear. To understand how epigenetic mechanisms work this project utilizes a simple organism, budding yeast. Yeast uses an epigenetic gene repression mechanism, known as silencing to control the genes responsible for determining cell type. The fundamental mechanisms of gene regulation and cell growth are remarkably similar in yeast and human cells; however, as it is far easier to perform many types of experiments using yeast, progress is more rapid using the yeast system. This project is focused on determining if the cell machinery responsible for duplicating and partitioning chromosomes as cells divide also has a role in establishing and maintaining silenced chromosomal structures. These studies will also examine the function of the Sir2 silencing protein in yeast. Interestingly, Sir2 proteins in many species affect lifespan, and there are several Sir2-like proteins in humans. Broader Impacts: The research pursuits described in this project will be closely integrated into the educational mission of Wesleyan University, an undergraduate-oriented liberal arts university. Projects in the principal investigator's laboratory on epigenetics are integrated into an advanced lab course required of undergraduate majors. This course is designed to familiarize undergraduates with the methods and approaches of the field in the context of pursuing novel research questions. Undergraduates (typically ~3/semester) also join the project leader's research lab, where they join a group of approximately three graduate students. The project leader is also collaborating in developing lessons in genetics with a local high school biology teacher; advanced students from this high school also visit the research lab to shadow graduate students.