Single-Molecule Human Nucleosome Spontaneously Ruptures under the Stress of Compressive Force: A New Perspective on Gene Stability and Epigenetic Pathways

Force manipulation on the biological entities from living cells to protein molecules has revealed many mechanical details of cell biology from resolving folding and unfolding pathways to finding molecular interaction forces. A nucleosome is the basic repeating unit of chromatin where the histone octamer is wrapped by DNA, important for gene stability and regulation. How the inner side of the DNA gets accessed by other DNA binding molecules has been a puzzle that has been intensively studied and debated, important to epigenetics, gene stability, and regulations. Here we report our observation of spontaneous ruptures of human nucleosomes under pico-Newton (pN) compressive force. The amplitude of the compressive force, a squeezing rather than pulling force, involved in our experiment is tens of pN, which can be thermally available by biological force fluctuation at room temperature and under physiological conditions. This kind of structural rupture can loosen up the DNA around the histone, which in turn makes the DNA accessible to transcription and epigenetic modifications.