Efficient chromatin accessibility mapping in situ by nucleosome-tethered tagmentation
Abstract
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.
Data availability
Sequencing data have been deposited in GEO under accession code GSE158327
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Efficient transcription-coupled chromatin accessibility mapping in situNCBI Gene Expression Omnibus, GSE158327.
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CUT&Tag for efficient epigenomic profiling of small samples and single cellsNCBI Gene Expression Omnibus, GSE124557.
Article and author information
Author details
Funding
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
- Roberto Bonasio, University of Pennsylvania, United States
Version history
- Received: September 19, 2020
- Accepted: November 13, 2020
- Accepted Manuscript published: November 16, 2020 (version 1)
- Version of Record published: December 7, 2020 (version 2)
Copyright
© 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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