Do you recommend performing size selection of the DNA during library preparation for CUT&RUN or ChIP-seq?

We do not recommend performing size selection of the DNA during library preparation for CUT&RUN or ChIP-seq. Based on our experience and feedback from customers, size selection can significantly decrease both the yield and diversity of the DNA library. If you are concerned about large DNA fragments >1 kb, then simply decrease the extension time when amplifying the adaptor-ligated DNA sample during the library preparation. We find that reducing the extension time to 10 to 15 seconds greatly reduces amplification of large fragments > 1kb, while being sufficient for amplification of smaller and more desirable DNA fragments during the CUT&RUN library preparation.

Last updated: October 6, 2025