Credit: AAAS

In eukaryotes, compaction of genomic DNA into dense chromosomes is the result of multiple levels of structural organization that are crucial for genome regulation and is orchestrated around the nucleosome basic units. Nucleosomes are made of 147 DNA bases tightly wrapped around an octameric protein core, composed of two copies of the histone proteins H2A, H2B, H3 and H4. Nucleosome arrays are arranged in a beads-on-a-string fashion, and fold into chromatin fibres, which then assemble into higher order structures. Finely tuned interaction forces between neighbouring nucleosomes drive chromatin formation and modulate the subsequent structural changes. While previous chromatin mechanical pulling experiments have measured the nucleosome interaction strengths, the details of the relative interaction potential, which would provide a better insight into the dynamic properties of chromatin, were missing. Now, J. J. Funke et al. present a molecular force spectrometer that can be used to access this information (Sci. Adv. 2, e1600974; 2016 ). The device consists of two DNA origami beams connected in a V shape, free to rotate around the hinge region under the attraction of two nucleosomes mounted on each beam. The origami platform allows very tight control over the relative nucleosome position and orientation, which is fundamental to unambiguously derive the interaction potential. Similarly to what happens in more traditional force spectroscopy experiments, the sample, in this case the origami device, can adopt a wide variety of conformations, characterized by specific aperture angles — the arms of the spectrometer are pulled together to different degrees depending on the extent of nucleosome attraction. Using single particle imaging with transmission electron microscopy (TEM) the authors count the number of spectrometers displaying a certain opening angle and reconstruct the free energy landscape for the nucleosome–nucleosome interaction based on the statistical distribution of the observed conformations. Their results suggest the existence of long-range weak nucleosome–nucleosome interactions and support the existence of a compliant, fluid-like chromatin state, in line with recent hypotheses and in sharp contrast with the classical model of a rigidly structured, linear chromatin. The TEM micrographs in the picture show a set of representative conformations of the spectrometers with nucleosome pairs anchored at 15 nm (top) and 30 nm (bottom) from the hinge (scale bars, 30 nm).