I would like to QC and analyze the fragment sizes of my CUT&Tag DNA before sequencing, but my yield is too low to see on an Agilent Bioanalyzer or TapeStation system. What should I do?

Due to the expected and typically low yield of CUT&Tag DNA, we recommend using all 30 µL of the CUT&Tag DNA sample (from section VI of the CUT&Tag protocol #77552) for library amplification. While CUT&Tag DNA libraries generated for histone modifications typically show some signal on the Agilent Bioanalyzer or TapeStation systems, libraries generated for non-histone proteins such as transcription factors and cofactors often have very weak or even no visible signal on Bioanalyzer systems, but they still generate NGS results with high-mapping rates, high numbers of identified binding peaks, and decent signal-to-noise ratios across the whole genome (see images).

We find that the High Sensitivity ScreenTape Assay, rather than the Standard ScreenTape Assay, on the TapeStation system provides a better method for CUT&Tag library quality assessment due to its optimized fluorescent chemistry and reduced baseline noise. For CUT&Tag libraries where the Bioanalyzer or the TapeStation systems cannot accurately determine the average library size, we recommend using an estimated size of 900 bp. This allows low-yield libraries to be intentionally pooled at a slightly higher proportion than normal-yield libraries.

Last updated: April 23, 2026