Each tiny cell in our body contains 2 meters of DNA. For
this to fit, the DNA needs to be very tightly packed. It is crucial
that this is done in such a way that the DNA can properly function.
A team of researchers from the Netherlands Cancer Institute has
uncovered the basic principles driving an important
packing-mechanism: the formation of loops. Their work was published
in Cell on May 4th.
The research groups involved include those of Benjamin Rowland
and Elzo de Wit; the first authors of the paper in Cell are Judith
Haarhuis and Robin van der Weide. Together, they set out to test a
model of DNA loop formation called the 'loop extrusion model', that
was proposed more than 15 years ago. In the loop extrusion model a
ring-shaped protein complex called cohesin plays a central
Cohesin is often found at the base of DNA loops. The idea of the
loop extrusion model is that cohesin is loaded onto small bumps in
the DNA by a complex known as SCC2/SCC4, after which cohesin
promotes the formation and enlargement of loops. According to the
model, as long as cohesin is attached, DNA can slide through the
ring, leading to increasingly larger loops. This will stop when a
protein called WAPL opens up the cohesin ring and releases it from
"Our data strongly suggest that this model actually is correct",
comments Rowland. "With a number of different experiments we have
shown that the longer cohesin embraces the base of the loop, the
larger the loops will get; that WAPL by releasing cohesin limits
the enlargement of loops; and that SCC2/SCC4 promotes loop
"What is also interesting, is that we noticed that without
WAPL, the loops continue to elongate beyond known natural barriers
consisting of CTCF proteins attached to the DNA.", says Rowland.
"Our findings therefore also tell us a lot about how these barriers
regulate the formation of loops. Disruption of loops can
affect gene regulation and therefore the cell's behavior. So the
proper formation of DNA loops is really important."
For the coming years the researchers will continue to
investigate the loop formation process, and what happens when the
loop formation goes wrong. Rowland: "It will be very exciting to
further study these processes, because they are fundamental to all
life on earth."