Rare yet specific interactions shape the 3D folding of chromatin

The organization of DNA in the three-dimensional space of the cell nucleus determines the regulation of most cellular activities. In recent years, a new level of organization has been discovered and its role in different pathologies has confirmed its critical importance. This level of organization rises from the preferential interaction between certain parts of the DNA and the exclusion of others. The mechanisms governing the assembly of these structures were still poorly understood.

In this study we labeled dozens of specific regions of DNA and quantified their interaction frequency using three-dimensional super-resolution microscopy. We have studied hundreds of Drosophila embryonic cells in different states of development and found that the frequency of each of these contacts changes according to cell type and its metabolic state. Next, we assessed whether these changes in interaction frequency were reflected at a larger scale of DNA organization by fluorescently labeling epigenetic markers of active and inactive chromatin.

From single molecule clusterization analysis, we have shown that DNA forms nano-compartments with distinct characteristics depending on whether chromatin is active or inactive and that the number and size of these compartments changes between different cell types. These results show that the regulation of the interaction frequency between specific regions plays a key role in the organization of chromatin at several scales. Other studies could reveal how alterations of these interactions could create pathological manifestations in the cell and also affect the development of a complete organism during embryogenesis.

This research has been recently highlighted in Nature Communications (Nature Communications, doi:10.1038/s41467-017-01962-x).