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CUT&Tag recovers up to half of ENCODE ChIP-seq histone acetylation peaks

Author

Listed:
  • Leyla Abbasova

    (UK Dementia Research Institute at Imperial College London
    Imperial College London)

  • Paulina Urbanaviciute

    (UK Dementia Research Institute at King’s College London
    King’s College London)

  • Di Hu

    (UK Dementia Research Institute at Imperial College London
    Imperial College London)

  • Joy N. Ismail

    (UK Dementia Research Institute at King’s College London
    King’s College London)

  • Brian M. Schilder

    (UK Dementia Research Institute at Imperial College London
    Imperial College London)

  • Alexi Nott

    (UK Dementia Research Institute at Imperial College London
    Imperial College London)

  • Nathan G. Skene

    (UK Dementia Research Institute at Imperial College London
    Imperial College London)

  • Sarah J. Marzi

    (Imperial College London
    UK Dementia Research Institute at King’s College London
    King’s College London)

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.

Suggested Citation

  • Leyla Abbasova & Paulina Urbanaviciute & Di Hu & Joy N. Ismail & Brian M. Schilder & Alexi Nott & Nathan G. Skene & Sarah J. Marzi, 2025. "CUT&Tag recovers up to half of ENCODE ChIP-seq histone acetylation peaks," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58137-2
    DOI: 10.1038/s41467-025-58137-2
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