Probing the Interaction Between Chromatin and Chromatin-Associated Complexes with Optical Tweezers

Single-molecule force spectroscopy is a powerful tool to analyze the architecture and interaction of large macromolecular assemblies that are refractory to high-resolution structural interrogations. Here, we describe an optical tweezers-based platform for extracting the mechanical fingerprints of individual nucleosome arrays bound with chromatin-associated complexes, such as the Polycomb repressive complex 2 (PRC2). This platform comprehensively characterizes the diverse binding modes of PRC2 on chromatin, measures their mechanical strengths, and is broadly applicable to the studies of other epigenetic machineries.