Researchers Develop qChIP-MS to Map Protein Networks on Human DNA

Scientists at NUS's Cancer Science Institute of Singapore (CSI Singapore) have created a novel technique that helps them understand how DNA is arranged and controlled within human cells.

Image credit: Billion Photos/Shutterstock.com

The research, published on May, 2026, in Nature Communications, presents a technique known as qChIP-MS that allows scientists to find protein groups that cooperate at particular DNA loci.

In human cells, DNA is enclosed in a structure called chromatin. Chromatin protects the DNA from harm, determines which genes are turned on or off, and influences how cells react to stress. Problems in chromatin regulation have been connected to cancer, the aging process, and other disorders. Since these protein networks help regulate gene activity and affect how cells behave in both health and disease, it is crucial to understand which proteins cluster at particular regions of the genome.

For years, researchers have depended on techniques that allow them to investigate one protein at a time. While these technologies have produced useful insights, they do not show the broader network of proteins operating together at a single position in the genome.

Our DNA is not controlled by a single protein acting alone. Instead, many proteins work together in coordinated complexes. We wanted to develop a practical way to see the full cast of players present at a specific region of our genome.

Dr. Yong Wai Khang, Study First Author, National University of Singapore

Mapping Protein Networks on Chromatin

The team created a single method known as qChIP-MS by combining two well-known technologies: mass spectrometry and chromatin immunoprecipitation. The technique allows scientists to identify the proteins linked to a specific chromatin region, enrich those regions, and quantify the abundance of those proteins.

Telomeres, the protective caps at the ends of chromosomes that are crucial to aging and cancer, were used by the researchers to validate the method. The technique proved to be applicable to many biological samples, such as tissues and certain genomic areas, and it was successful in identifying known telomere-associated proteins.

Importantly, the scientists devised ways to limit false-positive outcomes, a longstanding issue in chromatin-based research. They developed a more reliable method for analyzing complicated chromatin data by meticulously measuring the technique.

While qChIP-MS is largely a tool for research, its implications may be far-reaching. The method, by assisting scientists in understanding how proteins interact with chromatin in healthy and diseased cells, has the potential to speed discoveries in cancer biology and genome regulation, as well as inform future therapeutic strategies.

New Insights Into Cancer and Genome Regulation

The investigators are already using qChIP-MS to investigate how chromatin changes at telomeres in cancer cells. They are specifically looking at Alternative Lengthening of Telomeres (ALT), which allows some malignancies to keep their telomeres and continue to divide.

The team also intends to increase the sensitivity of the technology so that it may be utilized with fewer sample numbers and applied to more precise parts of the genome.

This work provides researchers with a new way to study how chromatin is organized and regulated. We hope it will become a useful addition to the toolbox for scientists investigating fundamental biology and diseases such as cancer.

Dennis Kappei, Assistant Professor and Principal Investigator, CSI Singapore

Asst Prof Kappei is also a faculty member at the Department of Biochemistry, and a Theme Co-Lead at NUS Centre for Cancer Research (N2CR), both within the NUS Yong Loo Lin School of Medicine.