The subtle interaction of cohesin and CTCF proteins to form loops in DNA





Image: Cees Dekker Lab / SciXel

In a publication published in Nature on April 19, Dutch and Austrian researchers shed new light on one of the mechanisms of loop formation in DNA. Loop extrusion plays an important role in structuring the genome and regulating gene expression, and the scientists have highlighted the influence of DNA tension in blocking or allowing loop formation.

DNA is a complex molecular structure found in nearly all cells that contains all the information needed to synthesize proteins, molecules that are essential for our body to function properly. When a protein needs to be produced, cells read and activate the genes, the sections of DNA, that contain the instructions for that specific protein.

During cell division, the long strands of DNA in eukaryotic cells are folded and compacted into the characteristic shape of chromosomes through DNA looping mechanisms. Also between divisions, DNA looping occurs and plays an important role in regulating which genes are read and activated.

Researchers from Cees Dekker’s lab at Delft University of Technology in the Netherlands and Jan-Michael Peters’ group at the Institute of Molecular Pathology in Vienna have shed new light on what controls the extrusion of DNA loops in eukaryotic cells when the cells are not dividing.

Image: Roman Barth, Cees Dekker Lab, TU Delft

The surprising role of DNA tension

They adopted a bottom-up approach, using only the minimal set of components for loop extrusion: DNA, the cohesin protein that extrudes loops into the DNA, and the DNA-binding protein CTCF that plays a  key role in determining where a loop begins and ends. They showed that the CTCF protein is sufficient to block the action of cohesin but that its impact depends strongly on the tension of the DNA.

DNA is under tension when other processes are occurring on the DNA. Cees Dekker explained that in the absence of tension, cohesin often ignores the CTFC protein, while “under the influence of DNA tension, CTCF becomes like a smart traffic light, allowing cohesin to pass or not, depending on the local traffic situation”.

What impact on synthetic cell research?

“Our work here is very fundamental, we are building knowledge about a complex system that does not exist in all cells. But it could help in the future to design more complex synthetic systems that need to fine-tune gene expression, said Roman Barth, PhD candidate in Dekker’s lab and member of the Dutch research program BaSyC (Building a Synthetic Cell), which aims to create an autonomous, self-reproducing synthetic cell with a bottom-up approach.

More info:

Related articles:

Queen Máxima and European Commissioner Mariya Gabriel visit synthetic cell researchers at TU Delft