DNA molecules in the cells‘ nuclei are neatly folded into loops. This serves to wrap them up tightly, but also to bring distant gene regulatory sequences into close contact. In a paper published this week by NATURE, scientists at the Research Institute of Molecular Pathology (IMP) in Vienna describe how cohesin might do the trick.
Twenty years ago, the protein complex cohesin was first described by researchers at the IMP. They found that its shape strikingly corresponds to its function: when a cell divides, the ring-shaped structure of cohesin keeps sister-chromatids tied together until they are ready to separate.
Schematic illustration of the loop-extrusion mechanism (Copyright: IMP)
Apart from this important role during cell-divison, other crucial functions of cohesin have been discovered since - at the IMP and elsewhere. One of them is to help fold the DNA, which amounts to about two meters per nucleus, into a compact size by way of creating loops. “We think that the cohesin-ring clamps onto the DNA-strand to hold the loops in place”, says IMP-director Jan-Michael Peters whose team worked on the project.
The chromatin-loops are not folded at random. Their exact shape and position play an important role in gene regulation, as they bring otherwise distant areas into close contact. “For a long time, scientists were mystified by how regulatory elements – the enhancers – are able to activate distant genes. Now we think we know the trick: precisely folded loops allow enhancers to come very close to the genes they need to regulate”, says Peters. Research results point to cohesin as mediator of this process. Jan-Michael Peters and his team have already shown that the cohesin complex accumulates in areas where loops are formed.
Several scientists recently proposed a so-called “loop-extrusion mechanism” for the folding of chromatin. According to this hypothesis, cohesin is loaded onto DNA at a random site. The DNA strain is then fed through the ring-shaped complex until it encounters a molecular barrier. This element, a DNA-binding protein named CTCF, acts much like a knot tied in a rope and stops the extrusion-process at the correct position. Defined genome-sequences that were previously located far apart are now next to each other and can interact to regulate gene expression.
In NATURE online this week, IMP-researchers publish data that support the existence of such a mechanism. First author Georg Busslinger, a PhD-student in Jan-Michael Peters’ team, showed in mouse cells that cohesin is indeed translocated on DNA over long distances and that the movement depends on transcription, suggesting that this may serve as a ‘motor’.
“The loop extrusion hypothesis has opened up a whole new research area in cell biology and we will probably see many more papers published on this topic in the future”, comments Jan-Michael Peters. Understanding cohesin-function is also relevant from a medical perspective since a number of disorders, including certain cancers, are associated with malfunctions of the protein-complex.
Busslinger GA, Stocsits RR, van der Lelij P, Axelsson E, Tedeschi A, Galjart N und Peters J-M: Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl. Nature Advance Online Publication, 19 April 2017, http://rdcu.be/rsMu.
A News-Feature on the topic was published by NATURE simultaneously: http://www.nature.com/news/dna-s-secret-weapon-against-knots-and-tangles-1.21838
An illustration can be downloaded and used free of charge in connection with this press release: https://www.imp.ac.at/news-media/downloads/
Caption: Schematic illustration of the loop-extrusion mechanism (Copyright: IMP)
About the IMP
The Research Institute of Molecular Pathology (IMP) in Vienna is a basic biomedical research institute largely sponsored by Boehringer Ingelheim. With over 200 scientists from 37 nations, the IMP is committed to scientific discovery of fundamental molecular and cellular mechanisms underlying complex biological phenomena. Research areas include cell and molecular biology, neurobiology, disease mechanisms and computational biology.
Research Institute of Molecular Pathology
+43 (0)1 79730 3625
Dr. Heidemarie Hurtl | idw - Informationsdienst Wissenschaft
Glycosaminoglycan-based hydrogels for a better treatment of chronic wounds
20.04.2017 | Leibniz-Institut für Polymerforschung Dresden e. V.
Action Required: Invasive Fungus Is Killing European Salamanders
20.04.2017 | Universität Zürich
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
20.04.2017 | Life Sciences
20.04.2017 | Earth Sciences
20.04.2017 | Health and Medicine