Researchers at Utrecht University have developed a widely applicable method to obtain insight into the interactions between proteins and chromatin at the atomic level. This is the complex of DNA and proteins in the cell that regulates everything pertaining to DNA, both during the development of the cell and over the course of its life. The method is new in that it also provides insight into the effects of the interaction on the local motions of the protein and the chromatin. “We still don’t know much about how this fundamental layer of biology works, because it is such a complex system”, according to Utrecht University research leader Dr. Hugo van Ingen. The method was published in the scientific journal Angewandte Chemie.
Chromatin acts as the gatekeeper for the genome: it either promotes or refuses access to the DNA, and therefore controls the processes in the cell. Regulatory proteins that bind to a specific location on the chromatin, influence the gatekeeper and thereby for example either activate or deactivate a gene. “The field of pharmaceutical research is interested in these kinds of interactions, because they can guide the development of new medications. However, we know only for a few proteins what the interaction with chromatin actually looks like”, Van Ingen explains.
NMR fingerprint of nucleosomes
The researchers use their new method to zoom in on the individual basic units of chromatin, called nucleosomes. These are mixed in a solution together with the protein to be studied such that they bind together. Using a centrifuge, the resulting nucleosome-protein complexes are then compressed into an extremely compact sample, which is similar to the chromatin in the cell. For comparison, a sample is also created using nucleosomes without the protein. A ‘fingerprint’ of the molecule is then generated using NMR spectroscopy, a kind of MRI scanner for molecules. The differences between the two fingerprints show how the protein is bound to the nucleosome.