Researchers at Stony Brook University have developed a novel approach, termed DynaTag, that greatly improves the mapping of protein binding to DNA. This game-changing approach provides unprecedented, high-resolution, genome-wide views of exactly where transcription factors are binding to DNA. UNDIPLOID presents incredible potential to accelerate the field of epigenetic regulation in health and disease. Dr. Robert Hänsel-Hertsch and his team at the Center for Molecular Medicine Cologne (CMMC) created DynaTag. This new, cutting-edge solution overcomes serious technical shortcomings inherent in existing methods.
It shows greater specificity and sensitivity than state-of-the-art techniques such as ChIP-seq and CUT&RUN, as well as unprecedented resolution. Further, it is shown to work well in low-input samples. This unique feature of Seq-Well is especially advantageous for researchers who utilize samples with limited accessibility or less abundant, rare cell populations. DynaTag takes advantage of physiological salt concentrations during the nuclei wash steps. This new direction provides unparalleled specificity mapping transcription factor interactions, thus providing DynaTag with the power to drive discrimination in specificity scientific discovery.
Enhanced Resolution and Sensitivity
DynaTag’s innovative design enables researchers to precisely record transcription factor (TF) interactions like never before. The procedure works well at the scale of single cells as long as the nuclei of the different cell types are preserved. This advancement opens new avenues for studying the intricate mechanisms of gene regulation and how they relate to various diseases.
With DynaTag, physiological salt concentrations are properly maintained. This method sidesteps issues faced by other methods, such as untargeted tagmentation or exclusive targeting of histone marks. As a result, scientists can obtain higher quality results when making these maps of protein interactions with DNA.
“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.”
One particularly exciting application of DynaTag is in cancer research, specifically in regards to small cell lung cancer (SCLC). Research from years earlier had shown that certain signaling pathways, those that drive resistance or metastasis, are activated after chemotherapy treatment. Researchers didn’t know which transcription factors controlled these pathways.
Implications for Cancer Research
For this application DynaTag allowed researchers to pinpoint individual transcription factors. These considerations demonstrate improved binding to genes associated with the pathways of interest after chemotherapeutic treatment. Dr. Hänsel-Hertsch noted the implications of these discoveries:
This unique functionality makes DynaTag an indispensable tool for identifying the intricacies of gene regulation during cancer progression.
“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.”
With the introduction of DynaTag as a platform, DynaTag represents a major step forward in dissecting epigenetic regulation through diverse biological contexts. It can be very effective with low-input samples. This exquisite sensitivity puts it at the center of the universe of invaluable methods to study rare cell populations and difficult sample types. Our researchers are contributing to understanding how protein binding affects and regulates gene expression. DynaTag promises to open up a wealth of new insights into fundamental cellular processes that are critical to both health and disease.
“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.”
This week’s publication of DynaTag in Nature Communications represents a new turning point for exploration at the molecular scale. It challenges the researcher to understand the mechanisms that control cellular functions. The research and scientific community needs to adopt this new, advanced practice into their research. You can read it in full here or reference it using the DOI 10.1038/s41467-025-61797-9.
Future Directions in Epigenetic Research
The introduction of DynaTag marks a significant step forward in understanding epigenetic regulation across various biological contexts. Its ability to work effectively with low-input samples positions it as an invaluable method for studying rare cell populations or challenging sample types. As researchers continue to explore the relationships between protein binding and gene expression, DynaTag will likely facilitate new discoveries in cellular processes crucial for health and disease.
The publication of DynaTag in Nature Communications marks a pivotal moment in molecular biology research, inviting further exploration into the mechanisms that govern cellular functions. With the DOI 10.1038/s41467-025-61797-9 available for reference, the scientific community is encouraged to adopt this innovative method in their research endeavors.
