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Topic Name: University of Toronto scientists successfully map entire yeast genome

Category: Genetic Engineering

Research persons: Corey Nislow

Location: University of Toronto, Canada

Details

University of Toronto scientists have devised a tool to help understand and predict the state of a cell by successfully mapping all 70,000 nucleosomes in yeast. Nucleosomes wrap DNA before it is transformed into proteins and are critical indicators and regulators of a cell’s state.

Led by Corey Nislow, a U of T Assistant Professor with the Banting and Best Department of Medical Research and Department of Molecular Genetics, the team created a complete, three-dimensional map of the yeast genome. This information was fed into a computer to build a software program that can predict where nucleosomes should be. The program worked remarkably well, and its accuracy will only improve with more data.

“When control is lost, cells make inappropriate proteins or divide inappropriately, which is what happens in diseases like cancer,” says Nislow, whose team worked closely with U of T Professor Timothy Hughes on the project. “Knowing where nucleosomes are is the first step in identifying what is going on in a cell and what the cell plans to do next, so this initial research could have big implications down the road for early detection of certain diseases.”

Scientists can tell by the presence of nucleosomes which genes are actively being converted into protein, and this information can function as an important first clue to disease detection.

Note for Nucleosomes

Nucleosomes are the fundamental repeating units of all eukaryotic chromatin (except when packaged in sperm). They package DNA into chromosomes inside the cell nucleus and control gene expression. They are made up of DNA and four pairs of proteins called histones, and resemble "beads on a string of DNA" when observed with an electron microscope. The nucleosome hypothesis proposed by Don and Ada Olins and Roger Kornberg in 1974, was a paradigm shift for understanding eukaryotic gene expression. The proteins that make up the nucleosome are called histones. Histones H2A, H2B, H3 and H4 are part of the nucleosome while histone H1 is the linker DNA between the two nucleosomes.
Nucleosomes appear to serve two major purposes within the cell nucleus. First, they provide the lowest level of compaction which is required to fit dsDNA (double-stranded DNA) into the cell nucleus. Secondly, they are important in the regulation of transcription by preventing RNA polymerase from unnecessarily accessing the promoter regions of genes which are not needed by the cell. If the requirements of the cell change, enzymes known as remodeling factors can remove or change the position of the nucleosome to allow access. Nucleosomes also appear to be major carriers of epigenetically inherited information.

Note for Yeasts

Yeasts are a growth form of eukaryotic microorganisms classified in the kingdom Fungi, with approximately 1,500 species described. Most reproduce asexually by budding, although a few do by binary fission. Yeasts are unicellular, although some species with yeast forms may become multicellular through the formation of a string of connected budding cells known as pseudohyphae, or true hyphae as seen in most molds. Yeast size can vary greatly depending on the species, typically measuring 3–4 µm in diameter, although some yeasts can reach over 40 µm.
Yeasts are chemoorganotrophs as they use organic compounds as a source of energy and do not require sun light to grow. The main source of carbon is obtained by hexose sugars such as glucose and fructose, or disaccharides such as sucrose and maltose. Some species can metabolize pentose sugars, alcohols, and organic acids. Yeast species either require oxygen for aerobic cellular respiration (obligate aerobes), or are anaerobic but also have aerobic methods of energy production (facultative anaerobes). Unlike bacteria, there are no known yeast species that grow only anaerobically (obligate anaerobes). Also, because they are adapted to them, yeasts grow best in a neutral pH environment.

About Researcher

Corey Nislow, PhD
Donnelly CCBR, #1210
160 College Street 
Toronto, Ontario M5S 3E1
Phone: 416-946-8351
Fax: 416-978-8287
corey.nislow@utoronto.ca