Profiling the epigenome at home

Steven Henikoff; Jorja G. Henikoff

Here we describe an at-home version of CUT&Tag in which all steps from mixing of native or lightly cross-linked nuclei with magnetic beads to post-PCR purification are performed in a single tube. This simplification of CUT&Tag requires only pipettors, a mini-centrifuge, a tube rotator, a PCR machine and disposable pipette tips, tubes and reagents to produce high-quality genome chromatin profiling data. During the COVID-19 physical distancing restrictions in Seattle we performed CUT&Tag@home for 16-32 samples per day with uniformly high quality for chromatin marks of active regulatory elements, gene bodies, Polycomb-silenced regions and constitutive heterochromatin. The low cell number requirements and read depths of CUT&Tag@home enable home-bound researchers to produce ready-for-sequencing barcoded libraries with relatively little technical expertise, effort or cost.