CUT&Tag for efficient epigenomic profiling of small samples and single cells

Hatice S. Kaya-Okur, Steven J. Wu, Christine A. Codomo, Erica S. Pledger, Terri D. Bryson, Jorja G. Henikoff, Kami Ahmad () and Steven Henikoff ()
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Hatice S. Kaya-Okur: Fred Hutchinson Cancer Research Center
Steven J. Wu: Fred Hutchinson Cancer Research Center
Christine A. Codomo: Fred Hutchinson Cancer Research Center
Erica S. Pledger: Fred Hutchinson Cancer Research Center
Terri D. Bryson: Fred Hutchinson Cancer Research Center
Jorja G. Henikoff: Fred Hutchinson Cancer Research Center
Kami Ahmad: Fred Hutchinson Cancer Research Center
Steven Henikoff: Fred Hutchinson Cancer Research Center

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Many chromatin features play critical roles in regulating gene expression. A complete understanding of gene regulation will require the mapping of specific chromatin features in small samples of cells at high resolution. Here we describe Cleavage Under Targets and Tagmentation (CUT&Tag), an enzyme-tethering strategy that provides efficient high-resolution sequencing libraries for profiling diverse chromatin components. In CUT&Tag, a chromatin protein is bound in situ by a specific antibody, which then tethers a protein A-Tn5 transposase fusion protein. Activation of the transposase efficiently generates fragment libraries with high resolution and exceptionally low background. All steps from live cells to sequencing-ready libraries can be performed in a single tube on the benchtop or a microwell in a high-throughput pipeline, and the entire procedure can be performed in one day. We demonstrate the utility of CUT&Tag by profiling histone modifications, RNA Polymerase II and transcription factors on low cell numbers and single cells.

Date: 2019
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DOI: 10.1038/s41467-019-09982-5

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