DNase I Digestion of Isolated Nulcei for Genome-Wide Mapping of DNase Hypersensitivity Sites in Chromatin

DNase I hypersensitivity (DHS) analysis is a powerful method to analyze chromatin structure and identify genomic regulatory elements. Integration of a high-throughput detection method into DHS analysis makes genome-wide mapping of DHS sites possible at a reasonable cost. Here we describe methods for DHS analysis carried out with mouse liver nuclei, involving DNase I digestion followed by isolation of DNase I-released DNA fragments suitable for high-throughput, next generation DNA sequencing (DNase-seq). A real-time PCR-based assay used to optimize DNase I digestion conditions is also described.