High efficiency targeted in situ genome-wide profiling

A method for detecting the binding of a chromatin-associated factor of interest to a sequence of chromatin DNA in a cell or nucleus, comprising:

• contacting a permeabilized cell or nucleus immobilized on a solid surface with a first specific binding agent that specifically recognizes the chromatin-associated factor of interest, wherein the first specific binding agent is coupled to a nuclease in an inactive state;
• activating the nuclease and cleaving DNA bound to the chromatin-associated factor of interest to thereby excise the DNA bound to the chromatin-associated factor of interest and release it to a supernatant;
• isolating the excised DNA in the supernatant;
• and
• determining the sequence of the excised DNA, thereby mapping binding of a chromatin-associated factor of interest to a sequence of DNA in the cell or nucleus.