A team led by Penn State's Ross Hardison, T. Ming Chu Professor of Biochemistry and Molecular Biology, has taken a large step toward unraveling how regulatory proteins control the production of gene products during development and growth. Working with collaborators including Drs. Mitchell Weiss and Gerd Blobel at Children's Hospital of Philadelphia, they focused specifically on the complex process of producing red blood cells (erythrocytes). These cells contain large amounts of hemoglobin, a molecule essential for transporting oxygen throughout the body. Abnormalities in hemoglobin figure in many serious diseases, such as sickle-cell disease, and abnormalities in producing blood cells can lead to leukemias. The work will be published in the December 2009 issue of the journal Genome Research.
As erythroid cells mature into red blood cells, the transcription factor, GATA-1, turns the genes responsible for making different proteins on and off. Hardison's team worked with a special strain of mouse erythroid cells that lack the gene gata-1. These cells could not mature into red blood cells unless the researchers added the protein GATA-1 experimentally. This procedure allows the investigators to monitor how the genes respond to GATA-1.
GATA-1 binds to special sites on the cell's DNA. The first step of the project was to locate the genes that are affected by GATA-1, so the researchers conducted a genome-wide search after adding GATA-1 to the cells. Using microarrays developed by newer methods of manufacturing which allow for a much higher density of probes, the team examined 19,000 mouse genes using 45,000 probe sets, many more than previous researchers had been able to study.
They found that adding GATA-1 affected 2,616 genes significantly, which was defined as showing at least a twofold change in the amount of the gene's product. Substantially more genes (1,568) were turned down or off by GATA-1 than were turned on (1,048) by GATA-
|Contact: Barbara K. Kennedy|