1. Chromosomes and Gene Expression
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Efficient chromatin accessibility mapping in situ by nucleosome-tethered tagmentation

  1. Steven Henikoff  Is a corresponding author
  2. Jorja G Henikoff
  3. Hatice S Kaya-Okur
  4. Kami Ahmad
  1. Fred Hutchinson Cancer Research Center, United States
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Cite this article as: eLife 2020;9:e63274 doi: 10.7554/eLife.63274


Chromatin accessibility mapping is a powerful approach to identify potential regulatory elements. A popular example is ATAC-seq, whereby Tn5 transposase inserts sequencing adapters into accessible DNA ('tagmentation'). CUT&Tag is a tagmentation-based epigenomic profiling method in which antibody tethering of Tn5 to a chromatin epitope of interest profiles specific chromatin features in small samples and single cells. Here we show that by simply modifying the tagmentation conditions for histone H3K4me2 or H3K4me3 CUT&Tag, antibody-tethered tagmentation of accessible DNA sites is redirected to produce chromatin accessibility maps that are indistinguishable from the best ATAC-seq maps. Thus, chromatin accessibility maps can be produced in parallel with CUT&Tag maps of other epitopes with all steps from nuclei to amplified sequencing-ready libraries performed in single PCR tubes in the laboratory or on a home workbench. As H3K4 methylation is produced by transcription at promoters and enhancers, our method identifies transcription-coupled accessible regulatory sites.

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Author details

  1. Steven Henikoff

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    Competing interests
    Steven Henikoff, S.H. has filed patent applications related to this work..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7621-8685
  2. Jorja G Henikoff

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    No competing interests declared.
  3. Hatice S Kaya-Okur

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    Hatice S Kaya-Okur, H.S.K. has filed patent applications related to this work..
  4. Kami Ahmad

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    No competing interests declared.


National Institutes of Health (R01 HG010492)

  • Steven Henikoff

National Institutes of Health (R01 GM108699)

  • Kami Ahmad

Chan Zuckerberg Initiative (Fred Hutch HCA Seed Network)

  • Steven Henikoff
  • Kami Ahmad

Howard Hughes Medical Institute (Henikoff)

  • Steven Henikoff

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Roberto Bonasio, University of Pennsylvania, United States

Publication history

  1. Received: September 19, 2020
  2. Accepted: November 13, 2020
  3. Accepted Manuscript published: November 16, 2020 (version 1)


© 2020, Henikoff et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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