Strong association between genomic 3D structure and CRISPR cleavage efficiency
Fig 6
Hypotheses explaining the inverse relation between genomic 3D density and CRISPR efficiency.
Unsuitable target sites are colored in orange, and suitable, fully complementary target sites are colored in green. pH/pL is the probability of binding to the suitable target site in the high-density/low-density region, respectively. (A) A Cas9-sgRNA complex searching for a target site in a dense region (left) encounters many unsuitable target sites; thus, the probability of finding the suitable target site in the dense region is lower than in a low-density region (right), where significantly fewer potential target sites exist. (B) Target sites in high-density regions (left) are less accessible physically to the Cas9-sgRNA complex, relative to low-density regions (right), because of DNA packing in the region.