By applying high-speed atomic-force microscopy (HS-AFM), Richard Wong and colleagues from Kanazawa University (NanoLSI WPI) provide valuable insights into the spatiotemporal dynamics of DNA-histone interactions.
The researchers looked at the interaction between DNA and a histone called H2A, one of the five main histones. To check the applicability of HS-AFM as a viable tool for imaging the DNA-histone interaction, they first focused on H2A in its native state. Wong and colleagues were able to image the topology of the molecule, and how it changes over time. Importantly, they showed that the HS-AFM process, during which a tapping force is constantly exerted on the molecule, does not lead to conformational changes or actual damage.
Wong and colleagues also investigated the effect of ionic strength on the DNA-histone binding affinity, by changing the salt concentration of the liquid containing the DNA-histone aggregate. When increasing the liquid's salinity, the aggregate was found to dissolve. When diluting the liquid again -- and so reducing the salt content -- the aggregate reformed. This result shows that varying the ionic strength (i.e., the salt concentration) of the environment of the DNA-H2A complex provides a way to mimic the variations in the strength of DNA-histone interactions as they happen in living organisms.
"[Our work] demonstrates ... the potential to study protein aggregation and protein-nucleic acid aggregate formation in various human diseases," the researchers said.
Photo: Dynamic inchworm-wrapping interactions between short-linearized dsDNA and histone H2A on a cationic lipid substrate captured using HS-AFM. Credit: Kanazawa University