Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have developed a new method called Gromit for studying gene regulation by employing a transposon, or jumping gene. Using Gromit they were able to study mice and found that the genome is not organized in a gene-centric manner and that gene expression is fine-tuned at the tissue level.
EMBL published their work online today in Nature Genetics. The paper is titled “Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor.”
The scientists engineered a jumping gene to react to the presence of regulatory elements. They also devised a method to control when it jumps to a different location in a mouse's genome. Through selective breeding, group leader François Spitz, Ph.D., and his colleagues were then able to generate lines of mice with the jumping gene in many different places. In each of these lines, the jumping gene gave them information about the regulatory activity happening in the area of the genome where it was sitting.
"This new technique is easier, faster, less invasive, and more efficient than previous approaches," according to Dr. Spitz. "We don't have to go through the complex and time-consuming process of engineering embryonic stem cells to create a mouse from. With Gromit we only have to mate the mice."
Gromit enables the systematic exploration of the part of the genome that does not code for proteins, the EMBL team notes. It allows researchers to easily delete or re-shuffle areas of the genome to assess their biological role, they add. This approach can be used to create mouse models in which to study human diseases.
Using Gromit Dr. Spitz’ group generated several hundred mice and embryos, each with a regulatory sensor inserted at a random genomic position. Scientists have thought that regulatory elements essentially controlled a specific gene or group of genes.
EMBL’s large sampling of the genome revealed the widespread presence of long-range regulatory activities along chromosomes, forming overlapping blocks with distinct tissue-specific expression potentials. The presence of tissue-restricted regulatory activities around genes with widespread expression patterns challenges the gene-centric view of genome regulation and suggests that most genes are modulated in a tissue-specific manner.