Table 2.

Troubleshooting.

Step	Problem	Possible reason	Solution
12 & Box 1	Editing efficiency is low	(i) low efficiency gRNA (ii) transfection efficiency is low	(i) rethink the design and choice of your gRNA (ii) optimize the transfection reagents and procedure for your cell type
33	Presence of unsheared DNA in sonicated samples	(i) Suboptimal sonication settings (ii) nuclei clumps present during sonication	(i) Optimize the settings by adding more cycles of sonication (ii) Make sure to obtain a single nuclei suspension before sonication (especially when working with crosslinked tissues)
59 & Box 2	Enrichment at on-target site is low	(i) Editing efficiency is low (ii) Low starting cell numbers	(i) see troubleshooting above (ii) Repeat experiment using recommended numbers of cells
76	Poor enrichment of the ChIP-Seq library and adapter dimer peak in fragment analyzer trace	(i) Input concentration of ChIP DNA into library prep too low (ii) presence of adapter dimers before library enrichment that compete with adapter-ligated DNA during the PCR	(i) Repeat experiment using recommended numbers of cells. If necessary pool ChIP DNA from multiple experiments. (ii) Perform DNA size selection of the adapter-ligated DNA fragments using SPRI beads, PippinPrep or separation by gel electrophoresis