ABSTRACT The overall mission of this Mapping Center is to create and disseminate open access, comprehensive, high-quality, high-resolution reference maps of DNase I hypersensitive sites (DHSs) in the human and mouse genomes, at previously unattainable levels of cellular and anatomical definition. Regulatory DNA is actuated in an exceptionally state-specific manner;; accordingly, achieving a comprehensive map of DHSs necessitates the interrogation of an expansive and finely partitioned range of cell and tissue samples. Progressive technical improvements and recent innovations have resulted in dramatic (>100x) decreases in requisite input biological sample quantities coupled with equally dramatic (>100x) increases in assay throughput, and corresponding decreases in the incremental cost of generating reference-quality DHS maps. These advances have in turn opened the possibility of systematically addressing all well-defined physiologically and disease-relevant anatomic and cellular compartments. Four major Specific Aims are targeted: (1) To create open access, comprehensive high-quality, high- resolution reference maps of human DNase I hypersensitive sites;; (2) To create and disseminate comprehensive high-quality, high-resolution reference maps of mouse DNase I hypersensitive sites;; (3) To maintain and disseminate reference indices of DNase I hypersensitive sites and footprints in the human and mouse genomes;; and (4) To enable large-scale intake of Consortium and Community samples for high-quality, high-throughput DHS mapping.