Better Way Found to Locate DNA Packing Proteins in Genome

A team of bioinformatics and experimental researchers have developed a more accurate way to mathematically predict the locations of the tiny protein spools that help package DNA in the cell nucleus.

The spools, called nucleosomes, also play a critical role in controlling gene activity, that is, whether or not a gene is turned on and actively involved in making a particular protein.

The spools occur all along the length of DNA. The DNA is wrapped roughly twice around each spool, with thousands of spools occurring along the DNA strand. The spools themselves are closely packed like beads on a string.

The study, published in a recent issue of Nature Genetics, was a collaboration between researchers at Ohio State University and Pennsylvania State University.

The investigators used common baker’s yeast to show that the spools are not randomly scattered throughout the genome, that is, the entire set of yeast genes, but that their positions are determined in part by the sequence of the DNA being packaged.

In addition, the researchers showed that some DNA sequences exclude the spools. These exclusion zones occur at the beginning of genes where proteins assemble to “read” the gene. The spools might encroach on the exclusions zones to turn genes off.

“Our study provides a new and more precise way to predict the locations of nucleosomes throughout the yeast genome, which might be applicable to animal and plant genomes as well,” says first author Ilya P. Loshikhes, assistant professor of biomedical informatics at the Ohio State University.

“DNA sequences that position nucleosomes were very hard to find in a sea of other DNA sequences,” says senior author B. Franklin Pugh, professor of biochemistry and molecular biology at the Pennsylvania State University, “so we had to determine their positions in several other yeast species to be sure we had found the right ones.”

By aligning the positions from the different species, the real positions stood out and the false positions faded away, he says.

“Knowing where nucleosomes reside has implications about where DNA regulatory regions will reside, and it will influence the three-dimensional structure of chromosomes,” Pugh says.

The researchers chose to study yeast, Ioshikhes says, because yeast cells have simple genomes that are far easier to study than humans.

“The structure of nucleosomes is basically the same in yeast and in humans,” he says, “so what we learn from yeast should help us better understand humans.”

Funding from the National Institute for General Medical Sciences supported this research.

Contact:

Darrell E. Ward, Medical Center Communications, 614-293-3737, or Darrell.Ward@osumc.edu