Over the last decade, researchers have identified dozens of regeneration genes in organisms like zebrafish, flies, and mice. For example, one molecule called neuregulin 1 can make heart muscle cells proliferate and others called fibroblast growth factors can promote the regeneration of a severed fin. Yet, what has not been explored are the regulatory elements that turn these genes on in injured tissue, keep them on during regeneration, and then turn them off when regeneration is done.

In this study, researchers wanted to determine whether or not these important stretches of DNA exist, and if so, pinpoint their location. It was already well known that small chunks of sequence, called enhancer elements, control when genes are turned on in a developing embryo. But it wasn't clear whether these elements are also used to drive regeneration.

They looked for genes that were strongly induced during fin and heart regeneration in the zebrafish and found that a gene called leptin b was turned on in fish with amputated fins or injured hearts. They scoured the 150,000 base pairs of sequence surrounding leptin b and identified an enhancer element roughly 7,000 base pairs away from the gene.

They whittled the enhancer down to the shortest required DNA sequence. In the process discovered that the element could be separated into two distinct parts: one that activates genes in an injured heart, and, next to it, another that activates genes in an injured fin. Fusing these sequences to two regeneration genes, fibroblast growth factor and neuregulin 1, to create transgenic zebrafish whose fins and hearts had superior regenerative responses after injury.

Finally, the researchers tested whether these "tissue regeneration enhancer elements" or TREEs could have a similar effect in mammalian systems like mice. Attaching one TREE to a gene called lacZ that produces a blue color wherever it is turned on, they found that it could activate gene expression in the injured paws and hearts of transgenic mice.

Authors suspect that there may be many different types of TREEs: those that turn on genes in all tissues; those that turn on genes only in one tissue like the heart; and those that are active in the embryo as it develops and then are reactivated in the adult as it regenerates.

http://today.duke.edu/2016/04/genetrees