by Alice Park
October 19, 2015
It turns out the human genome can be snipped and tucked and
manipulated surgically, just like any organ
Ever since the human genome was
mapped in 2001, scientists have been
finding new and novel ways to manipulate it: intervening to remove
offending genes or DNA sequences that can contribute to disease, and
fixing mutations that can affect people's health.
As remarkable as those advances have
been, however, they have only occurred on one dimension - the linear
sequence of DNA.
Now scientists report in the Proceedings of the National Academy of
Sciences their success in manipulating the genome in 3D. The human
genome that's squeezed into every microscopic cell in the body
measures more than two meters long. To stuff it into a space just a
few microns wide (the human hair, by comparison, is 40 to 50 microns
in diameter) requires some masterful origami-like transformation.
In the study, Erez Lieberman Aiden, director of the center
for genome architecture at Baylor College of Medicine and Rice
University, and his colleagues describe how DNA performs this
It turns out that there is a sequence in
the genome - a DNA "word" - that signals when a long string of DNA
should turn and form a loop.
The end of that loop is signaled by the
same word but in reverse, a mirror image of the original. Where
these matched-up words appear on the genome determines which genes
are exposed in a relatively accessible place and therefore which
genes are more active.
Loops formed in cells in the heart, for
example, will be different from ones generated in skin cells or bone
"We have the same genome in all of
our cells, yet cells perform totally different functions," says
"That has to do with the fact that
different genes are on and off in different cells. How that is
managed is in part by the loops of DNA that they form.
an origami-like situation - you start with a blank sheet of
paper, but whether you can fold that into a hat, plane or crane
is a matter of folds. And its function - as a hat, plane or
crane - also depends on those folds."
Not only did Aiden and his colleagues
discover the way that loops form, they also conducted experiments to
show that they can manipulate where these loops form and potentially
change which genes are active and which are silent in specific
Beckwith-Wiedemann syndrome, for
example, may be partly explained by such abnormalities in the way
Children born with the condition tend to
be larger than their peers and develop larger abdomens due to
differences in the way that certain genes inherited from both
parents on chromosome 11 are expressed.
These findings hint at the potential of treating such conditions,
although more work has to be done to better understand how 3D
factors affect genetic diseases.
But combining the ability to change DNA
sequences in both a linear way, as well as a three-dimensional way,
could provide a rich new way of treating certain diseases.
"By changing the way the DNA is
folded, we can change what the genome is doing," says Aiden. "We
can change the function of a cell. In many cases there are
multiple ways of getting a condition, and one of them might be