CUT&Tag recovers up to half of ENCODE ChIP-seq histone acetylation peaks
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
DNA-protein interactions have traditionally been profiled via chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq). Cleavage Under Targets & Tagmentation (CUT&Tag) is a rapidly expanding technique that enables the profiling of such interactions in situ at high sensitivity. However, thorough evaluation and benchmarking against established ChIP-seq datasets are lacking. Here, we comprehensively benchmarked CUT&Tag for H3K27ac and H3K27me3 against published ChIP-seq profiles from ENCODE in K562 cells. Combining multiple new and published CUT&Tag datasets, there was an average recall of 54% known ENCODE peaks for both histone modifications. We tested peak callers MACS2 and SEACR and identified optimal peak calling parameters. Overall, peaks identified by CUT&Tag represent the strongest ENCODE peaks and show the same functional and biological enrichments as ChIP-seq peaks identified by ENCODE. Our workflow systematically evaluates the merits of methodological adjustments, providing a benchmarking framework for the experimental design and analysis of CUT&Tag studies.
Date Issued
2025-03-27
Date Acceptance
2025-03-13
Citation
Nature Communications, 2025, 16
ISSN
2041-1723
Publisher
Nature Portfolio
Start Page
2993
Journal / Book Title
Nature Communications
Volume
16
Issue
1
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40148272
PII: 10.1038/s41467-025-58137-2
Subjects
Humans
Histones
Chromatin Immunoprecipitation Sequencing
Acetylation
K562 Cells
High-Throughput Nucleotide Sequencing
Chromatin Immunoprecipitation
Publication Status
Published
Coverage Spatial
England
Article Number
2993
Date Publish Online
2025-03-27