design: The DNase Hi-C library preparation begins with cross-linking cells with formaldehyde to preserve the 3D chromatin architecture, followed by nuclei permeabilization and controlled chromatin digestion using DNase I instead of traditional restriction enzymes. This sequence-independent digestion allows for a more uniform coverage of the genome and higher resolution by overcoming the limitations of restriction site distribution. After digestion, the DNA ends are repaired and labeled with biotinylated nucleotides, followed by proximity ligation to join physically interacting fragments. The cross-links are then reversed, the DNA is sheared, and the biotin-labeled chimeric junctions are selectively captured using streptavidin beads for subsequent adapter ligation and high-throughput sequencing.