Electrophoretic stretching and imaging of single native chromatin fibers in nanoslits

Stretching single chromosomal DNA fibers in nanofluidic devices has become a valuable tool for studying the genome and more recently the epigenome. Although nanofluidic technology has been extensively used in single molecular DNA analysis, compared to bare DNA, much less work has been done to elongate chromatin, and only a few studies utilize more biologically relevant samples such as native eukaryotic chromatin. Here, we provide a method for stretching and imaging individual chromatin fibers within a micro- and nanofluidic device. This device was used to electrophoretically stretch and image single native chromatin fibers extracted from human cancer cells (HeLa cells) by attaching the chromatin to microspheres held at the entrance of a nanoslit. To further demonstrate the potential of this device in epigenetics, histone modification H3k79me2 was optically detected by fluorescence microscopy.