DNA Switches Controlling Whole-Body Regeneration Identified

DNA Switches Controlling Whole-Body Regeneration Identified

Researchers have identified genetic switches that activate a master gene for whole-body regeneration, which in turn activates various other genes involved in the growth response.

Some animals have the ability to regrow a limb or tail after it has been lost while others, such as planarian worms and sea anemones, are capable of much more impressive feats of regeneration. They can regain their normal shape and size after they have been cut in half. Unlocking the mystery behind these impressive regenerative feats could be of major importance to the field of regenerative medicine.

The researchers studied the three-banded panther worm and identified a section of non-coding DNA which is responsible for activating a master control gene which they termed early growth response (EGR). EGR can switch other genes involved in the regeneration process on and off and acts as a DNA switch to control the regeneration process.

In order to understand the process, the first major step was to sequence the entire genome, something that had not previously been done with any animal in the phylum. The full genome has now been sequenced and released.

The animals particularly useful for studies on regeneration. They have an important phylogenetic position in terms of their relations to other animals, so their study allows statements to be made about evolution. The animals are also easy to handle and survive well in the lab and more tools can be used in their study than other more sensitive animals.

The researchers explained that under normal circumstances, parts of the worm genome are tightly packed and folded, but by unfolding the DNA more areas are made available for activation. The researchers found that during the regeneration process the genome changes shape and parts open and close allowing activation of genes to occur. In total, around 18,000 regions of the genome change during the regeneration process but if the master gene is not activated, none of the changes will occur.

Humans may not have the ability to regrow a limb after an accident, but humans do have a gene that is very similar to EGR. Mansi Srivastava, assistant professor of organismic and evolutionary biology at Harvard university and head of the research team explained that if human cells are subjected to stress mechanically or with toxins, they express the human version of the EGR gene straightway.

“What EGR is talking to in human cells may be different than what it is talking to in the three-banded panther worm,” said Srivastava. “We want to figure out what those connections are, and then apply that to other animals, including vertebrates that can only do more limited regeneration.”

The researchers are now investigating whether the DNA switches they have identified are the same that are used during development and are continuing to investigate the precise nature of EGR gene and the regeneration process.

The research is detailed in the paper – Acoel genome reveals the regulatory landscape of whole-body regeneration – which was recently published in the journal Science. DOI: 10.1126/science.aau6173

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