DynaTag for efficient mapping of transcription factors in low-input samples and at single-cell resolution

Pascal Hunold, Giulia Pizzolato, Nadia Heramvand, Laura Kaiser, Giulia Barbiera, Olivia Ray, Roman Thomas, Julie George, Martin Peifer and Robert Hänsel-Hertsch ()
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Pascal Hunold: University of Cologne
Giulia Pizzolato: University of Cologne
Nadia Heramvand: University of Cologne
Laura Kaiser: University of Cologne
Giulia Barbiera: Genevia Technologies Oy
Olivia Ray: University of Cologne
Roman Thomas: University of Cologne
Julie George: University of Cologne
Martin Peifer: University of Cologne
Robert Hänsel-Hertsch: University of Cologne

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Systematic discovery of transcription factor (TF) landscapes in low-input samples and at single cell level is a major challenge in the fields of molecular biology, genetics, and epigenetics. Here, we present cleavage under Dynamic targets and Tagmentation (DynaTag), enabling robust mapping of TF-DNA interactions using a physiological salt solution during sample preparation. DynaTag uncovers occupancy alterations for 15 TFs in stem cell and cancer tissue models. We highlight changes in TF-DNA binding for NANOG, MYC, and OCT4, during stem-cell differentiation, at both bulk and single-cell resolutions. DynaTag surpasses CUT&RUN and ChIP-seq in signal-to-background ratio and resolution. Furthermore, using tumours of a small cell lung cancer model derived from a single female donor, DynaTag reveals increased chromatin occupancy of FOXA1, MYC, and the mutant p53 R248Q at enriched gene pathways (e.g. epithelial-mesenchymal transition), following chemotherapy treatment. Collectively, we believe that DynaTag represents a significant technological advancement, facilitating precise characterization of TF landscapes across diverse biological systems and complex models.

Date: 2025
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DOI: 10.1038/s41467-025-61797-9

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