Researchers at the University of Debrecen have identified a new mode of regulation that determines how genes function. In the long term, the discovery may lay the foundation for more targeted treatment of pathological conditions such as inflammation and cancer. The groundbreaking results were published in a prestigious international scientific journal, and the research was also recognized with the Publication Award of the University of Debrecen and the István Tisza Foundation for the University of Debrecen.
The aim of the research was to study the processes that determine how genes work. The key players in these processes are regulatory elements—short DNA sequences—that do not encode proteins but carry important information. Special proteins known as transcription factors bind to these elements, and together they determine how active a gene will be. The investigation was carried out on bone marrow macrophage cells from mice in order to better understand the regulatory system.
“Mouse bone marrow macrophages, which are immune cells, are widely used to model tissue macrophages. For this reason, in recent years a vast amount of next-generation sequencing data has been generated from this cell type, making it possible to study different levels of gene regulation. Since our research group also contributed to expanding and bioinformatically analyzing these datasets, it was a natural choice to examine the DNA element–based foundations of gene regulation in this model,” explained Gergely Nagy, research associate at the Institute of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen.
The bioinformatics analyses were performed using the institute’s supercomputer. The investigations included modifications of DNA sequences, their accessibility, protein binding, RNA transcription and quantity, and—where possible—comparisons of RNA and the corresponding protein levels. In addition, DNA–transcription factor interactions helped identify the regulatory elements accessible in macrophages, which were then classified based on their base sequence and other properties.
During the studies, the researchers discovered a new type of promoter that is specific to macrophages. The research began in the summer of 2020 within the framework of Gergely Nagy’s OTKA grant, and the results were published in early 2024 in Nucleic Acids Research, a leading Q1-ranked journal in the field of biochemistry and molecular biology.
“Our work was published in such a prestigious journal because the macrophage-specific regulatory element map revealed a type of gene-regulatory region (promoter) unique to macrophages that had not been identified before. These promoters differ both in composition and function from previously described promoter types. Their role is to ensure the characteristic gene expression pattern of the given cell type, and ultimately to maintain the identity of the cells,” emphasized Gergely Nagy.
In addition to Gergely Nagy, several members of Professor László Nagy’s research group also contributed to the study. Petros Tzerpos and Tímea Silye-Cseh took part in earlier experiments, while Dóra Nagy-Bojcsuk assisted with the bioinformatics analyses.
“Our research is basic science; it was not aimed directly at curing diseases. However, our discovery may help us better understand what happens under pathological conditions in the future. In our publication, we shared our knowledge about the regulatory elements we identified with the scientific community, so that our results may later be used for therapeutic purposes, in the development of new treatments,” added the University of Debrecen researcher.
The publication earned the Publication Award of the University of Debrecen and the István Tisza Foundation for the University of Debrecen.
“Receiving this award is confirmation and encouragement to continue our research. It is especially valuable to us because it recognizes a discovery that is the result of many years of dedicated work,” highlighted Gergely Nagy.
The researchers are continuing their investigations even after the publication. While the published article focused exclusively on results obtained from untreated, resting macrophages, their current research examines the effects of the anti-inflammatory interleukin-4 on gene regulation.
(unideb.hu)
