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Mapping technique can detect binding of proteins to DNA at single-cell resolution

New method for mapping protein binding to DNA
Schematic illustration showing that only DynaTag captures TF interactions by using physiological salt concentrations (110 mM KCl, 10 mM NaCl, 1 mM MgCl2) during nuclei wash steps. In contrast, the use of 150 mM NaCl or 300 mM NaCl or KCl lead to untargeted tagmentation or allows only for the targeting of histone marks, respectively. Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-61797-9

The binding of proteins to DNA is crucial for producing other proteins, ensuring that all the necessary processes in cells are performed, and for switching genes on or off. Proteins that bind to DNA are called transcription factors. Due to the dynamic interactions of transcription factors with DNA, it is difficult to determine where in the genome transcription factor–DNA interactions occur.

A research team at the University of Cologne has now developed the DynaTag method, which reliably identifies these interactions. If the are intact, DynaTag has proven effective with low-input samples and even at the level of the individual cell. The study, "DynaTag for efficient mapping of in low-input samples and at ," is in Nature Communications.

"DynaTag outperforms existing methods such as ChIP-seq and CUT&RUN in terms of sensitivity and resolution of results. The new method delivers high-resolution mapping of the DNA regions where transcription factors bind," says Dr. Robert Hänsel-Hertsch, Principal Investigator at the Center for Molecular Medicine Cologne (CMMC) and leader of the study.

In such as animals with different tissues and cell types, it is difficult to identify where transcription factors bind to DNA in the genome. According to the researchers, this new method, which enables the analysis of single cells across various tissues, could therefore significantly enhance our understanding of developmental biological processes and disease mechanisms in physiologically relevant systems.

In addition, the method can identify the activity of transcription factors in tissue samples. This is significant for , as are routinely obtained from patients for pathological examination.

The researchers demonstrated the method's advantages in a study on in a mouse model. The research group led by Hänsel-Hertsch examined the binding of transcription factors in small cell lung tumors before and after the administration of chemotherapy.

"It had already been established that certain signaling pathways promoting resistance or metastasis are activated after chemotherapy in small cell lung cancer. However, it was not known which transcription factors regulate these signaling pathways," says Hänsel-Hertsch.

"With the help of DynaTag, we were able to identify specific transcription factors that show increased binding to genes belonging to these signaling pathways after chemotherapy and are likely to promote further tumor growth."

DynaTag thus addresses a fundamental technical limitation and opens up new avenues for studying epigenetic regulation in health and disease—particularly in samples that are difficult to access or in rare cell populations.

More information: Pascal Hunold et al, DynaTag for efficient mapping of transcription factors in low-input samples and at single-cell resolution, Nature Communications (2025).

Journal information: Nature Communications

Provided by University of Cologne

Citation: Mapping technique can detect binding of proteins to DNA at single-cell resolution (2025, July 28) retrieved 28 July 2025 from /news/2025-07-technique-proteins-dna-cell-resolution.html
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