12 March 2015 ICFO in Cell

Comparison between an image of the nucleus of a cell obtained with the STORM technique and one obtained with conventional microscopes

Top picture (from left to right): CRG researchers Maria Aurelia Ricci and Pia Cosma; Bottom picture (from left to right): ICFO researchers Carlo Manzo, Melike Lakadamyali and María García-Parajo.

Super-resolution microscopes reveal the link between Genome Packaging and Cell Pluripotency Until now it was known that our DNA is packaged by regular repeating units of the nucleosomes throughout the genome which give rise to chromatin. However, due to the lack of suitable techniques and instruments, the chromatin organization inside a cell nucleus could not be observed in a non-invasive way with sufficient resolution.

Now, for the first time, ICFO researchers Dr. Carlo Manzo, ICFO Prof. Melike Lakadamyali and ICREA Prof at ICFO María García-Parajo, in collaboration with researchers Maria Aurelia Ricci and Prof. Pia Cosma from CRG- Centre for Genomic Regulation, have been able to visualize and even count the smallest units which, packaged together, form our genome. This study was possible thanks to the use of super-resolution microscopy, a new cutting-edge optical technique that received the Nobel Prize in Chemistry in 2014. In combination with innovative quantitative approaches and numerical simulations, they were also able to define the genome architecture at the nano-scale. Most importantly, they found that the nucleosomes are assembled in irregular groups across the chromatin and that nucleosome-free-DNA regions separate these groups.

What the scientists have found is that DNA is not regularly packaged with nucleosomes. Instead they have seen that nucleosomes are assembled in groups of varying sizes, called “nucleosome clutches” -because of their similarity to egg clutches. They found that pluripotent stem cells have, on average, clutches with less density of nucleosomes. In addition, clutch size is related to the pluripotency potential of stem cells, meaning that the more pluripotent a cell is, the less nucleosomes are included in its clutches.

Even though all the cells in our body have the same genetic information, they do not express all the genes at the same time. When a cell specializes, some of the DNA regions are silenced or less accessible to the molecule that reads the genome: the RNA polymerase. Depending on the specialisation of the cells, different levels of DNA packaging will occur. This new work published in the prestigious journal Cell, establishes a new understanding of how the chromatin fibre is assembled and packaged forming a specific DNA structure in every cell.