[pchealth] Harvard University uncovers DNA switch that controls genes for whole-body regeneration

Lawrence London lfljvenaura at gmail.com
Fri Mar 15 18:59:47 EDT 2019


Harvard University uncovers DNA switch that controls genes for whole-body

Humans may one day have the ability to regrow limbs after scientists at
Harvard University uncovered the DNA switch that controls genes for
whole-body regeneration.

Some animals can achieve extraordinary feats of repair, such as salamanders
which grow back legs, or geckos which can shed their tails to escape
predators and then form new ones in just two months.

Planarian worms, jellyfish, and sea anemones go even further, actually
regenerating their entire bodies after being cut in half.

Now scientists have discovered that that in worms, a section of non-coding
or ‘junk’ DNA controls the activation of a ‘master control gene’ called
early growth response (EGR) which acts like a power switch, turning
or off.

“We were able to decrease the activity of this gene and we found that if
you don't have EGR, nothing happens," said Dr Mansi Srivastava, Assistant
Professor of Organismic and Evolutionary Biology at Harvard University.

“The animals just can't regenerate. All those downstream genes won't turn
on, so the other switches don't work, and the whole house goes dark,

The studies were done in three-banded panther worms. Scientists found that
during regeneration the tightly-packed DNA in their cells, starts to
unfold, allowing new areas to activate.

But crucially humans also carry EGR, and produce it when cells are stressed
and in need of repair, yet it does not seem to trigger large scale

Scientists now think that it master gene is wired differently in humans to
animals and are now trying to find a way to tweak its circuitry to reap its
regenerative benefits.

Post doctoral student Andrew Gehrke of Harvard believes the answer lies in
the area of non-coding DNA controlling the gene. Non-coding or junk DNA was
once believed to do nothing, but in recent years scientists have realised
is having a major impact.

“Only about two percent of the genome makes things like proteins," added Mr
Gehrke said. “We wanted to know: What is the other 98 percent of the genome
doing during whole-body regeneration?

“I think we've only just scratched the surface. We've looked at some of
these switches, but there's a whole other aspect of how the genome is
interacting on a larger scale, and all of that is important for turning
genes on and off.”

Marine animals, such as the moon jellyfish, are masters of regeneration
some have been found to clone themselves after death.

In 2016, a Japanese scientist reported that three months after the death of
his pet jellyfish, a sea anemone-like polyp rose out of the degraded body,
and then astonishingly aged backwards, reverting to a younger state.

In the 1990s, scientists in Italy discovered that the Turritopsis dohrnii
jellyfish switches back and forth from being a baby to an adult, resulting
in its nickname, the immortal jellyfish.

Dr Srivastava added: “The question is: If humans can turn on EGR, and not
only turn it on, but do it when our cells are injured, why can't we
regenerate?" added Dr Srivastava.

"It's a very natural question to look at the natural world and think, if a
gecko can do this why can't I?

“The answer may be that if EGR is the power switch, we think the wiring is
different. What EGR is talking to in human cells may be different than what
it is talking to in the three-banded panther worm.”

The research was published in the journal Science

A master regulator of regeneration

   1. Michael Alonge1
   2. Michael C. Schatz1

See all authors and affiliations
Science  15 Mar 2019:
Vol. 363, Issue 6432, pp. 1152-1153
DOI: 10.1126/science.aaw6258



*Hofstenia miamia*, commonly called the three-banded panther worm, is a
small flatworm that can be found along the shores of the Caribbean and
other warm waters. It is known for its impressive regenerative
capabilities, including the ability to regenerate any body part within a
few days of amputation. Previous reports identified some of the molecular
signals used to coordinate regeneration (*1*), although the specific genes
and gene networks that regulate this response were unknown. On page 1191 of
this issue, Gehrke *et al.* (*2*) developed an impressive collection of
genomic resources for the species, including extensive DNA, RNA, and
chromatin accessibility data to promote *H. miamia* as a new model system
for studying regeneration. Using these data, they identify early growth
response (*Egr*), which encodes a candidate pioneer transcription factor
responsible for regulating the molecular regenerating response to wounding.

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