When it comes to regeneration, some animals are able to perform amazingly well. If you cut off a salamander's leg, it will regrow. When threatened, some geckos drop their tails for distraction and later grow up again.
Other animals continue the process. Planarian worms, jellyfish and sea anemones can regenerate their entire body after being cut in half, revealing a series of DNA switches that seem to control genes for whole-body regeneration. The study was described in a paper dated March 15 in Science .
Srivastava and Andrew Gehrke, a postdoctoral researcher working in their lab, found three-banded Panther worms to test the process A section of non-coding DNA controls the activation of a "major control gene" called early growth response or EGR becomes. When EGR is active, it controls a number of other processes by turning other genes on or off.
"What we discovered is that this creates a master gene … and this activates genes that are activated during regeneration," said Gehrke. "Basically, it's about the noncoding regions getting the coded regions to turn on or off, so it's a good way to imagine them as switches."
For this process to work, Gehrke said the dwarf cell DNA, which is normally tightly folded and compressed, has to change and make new areas available for activation.
"Many of these very tightly packed parts of the genome actually become physically more open because there are regulatory switches that need to turn genes on or off," he said. "One of the big insights in this article is that the genome is very dynamic and really changes during regeneration when different parts open and close."
But before Gehrke and Srivastava understood the dynamics of the worm genome, they had to put together their own sequence ̵
"This is a big part of this work – we release the genome of this kind, which is important because it is the first of this strain," Srivastava said. "So far, no complete genome sequence was available."
And it's also remarkable, she said, because the tripartite Pantherworm represents a new model system for the study of regeneration.
"Previous work on other species helped us learn many things about regeneration," she said. "However, there are some reasons to work with these new worms, one of which is that they are in an important phylogenetic position, and as they are related to other animals … … we can make statements about Evolution. [19659003"Theotherreasonisthatlarge-scalelabsare"Ifoundtheminmypostdoctoralresearchfieldseveralyearsagoandhavebeenopentomanyothertools"
And while these tools can demonstrate the dynamic nature of the genome during regeneration, Gehrke was able to identify up to 18,000 regions that change – which is important to them How much importance could he draw from her investigation.
The results show that the EGR acts as a regeneration power switch – once it is turned on, other processes can run but without them. nothing happens.
"We were able to reduce the activity of this gene and we found that if you do not have Egr, nothing happens," Srivastava said. "The animals just can not regenerate, all these downstream genes will not turn on, so the other switches will not work, and the whole house will basically be dark."
While the study reveals new information about how the process works in worms, it can also help explain why it does not work in humans.
"It turns out that Egr, the master gene, and the other genes that are turned on and off downstream are present in other species, including humans," Gehrke said.
"The reason why we called this gene Egr in the worms is that, looking at its sequence, it resembles a gene that has already been studied in humans and other animals," Srivastava said. "If you have human cells in a bowl and they emphasize, be it mechanically or putting toxins on them, they will immediately express Egr.
" But the question is: if humans can turn on Egr, and not just turn it off But if you do it, if our cells are injured, why can not we regenerate? "Srivastava said. The answer could be, if EGR is the power switch, we think the wiring is different. What addresses EGR in human cells may be different from what it speaks in the three-band Pantherworm, and what Andrew did with this study has found a way to get at this wiring. We want to find out what these compounds are and then apply them to other animals, including vertebrates, who can only do more limited regeneration. "
Srivastava and Gehrke hope that they will investigate whether the genetic switches are activated during regeneration are the same as in development and to continue working to better understand the dynamic nature of the genome.
" Now, since we know which switches are for regeneration, we look at the switches involved in the development and whether they are the same, "Srivastava said. Are you just developing again, or is another process involved?
The team is also working to understand how EGR and other genes activate the regeneration process, both for three-handed panther worms and for other species.
In the end, according to Srivastava and Gehrke, the study does not just emphasize value for understanding of the genome, but also for understanding the whole genome – the non-coding as well as the coding parts.
"Only about two percent of the genome make things like proteins," Gehrke said. "We wanted to know: what to do the other 98 percent of the genome during whole body regeneration? People have known for some time that many disease-causing DNA alterations are in noncoding regions … but not enough was paid for a process like whole body regeneration.
"I think we just scratched the surface," he continued. "We looked at some of these switches, but there is another aspect of genome interaction on a larger scale, not just how parts open and close, and all that is important to turn genes on and off, I think "There are several layers of this regulatory nature."
"It's a very natural question to look at in the natural world and think if a gecko can do that, why can not I," Srivastava said. There are many species that can regenerate, and others that can not, but it turns out when you compare genomes across all animals. Most of the genes we have are also present in the tripartite pantherworm … So, we think that some of these answers will probably not depend on whether certain genes are present or not, but on how they are interconnected or networked, and this answer can only be answered au s are from the noncoding part of the genome.
This research was supported with funding from the Milton Fund of Harvard University, the Searle Scholars Program, the Smith Family Foundation, the National Science Foundation, the Helen Hay Whitney Foundation, the Human Frontier Science Program, the National Institutes of Health the Biomedical Big Training Program, UC Berkeley, the Marthella Foskett Brown Chair of Biological Sciences, and the Howard Hughes Medical Institute.