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The specific objective of this research project was to investigate the processes that determine the functioning of genes. The key players in these processes are regulatory elements, which represent short DNA segments that do not encode proteins yet carry important information. There are special proteins, which are called transcription factors and which bind to these elements to determine together how active a gene indeed is. The experiments were conducted on bone marrow macrophage cells from mice in order to better understand the regulatory system.

“Mouse bone marrow macrophages, which are immune cells commonly used to model tissue macrophages, have been the subject of a large amount of next-generation sequencing data in recent years, enabling the study of various levels of gene regulation. Since our research group has also participated in the accumulation and the bio-informatic analysis of these data, it was obvious for us to use this model to study the DNA-determined basis of gene regulation,” said Gergely Nagy, a research fellow at the Institute of Biochemistry and Molecular Biology, Faculty of Medicine, 91��Ƶ��. 

The bio-informatic analyses were then performed by the supercomputer of the Institute of Biochemistry and Molecular Biology. Overall, the studies covered modifications to DNA segments, their accessibility and binding by proteins, RNA transcription and quantity and, where possible, comparisons of RNA and protein quantities derived from it. In addition, DNA transcription factor interactions identified accessible elements in macrophages, which were then classified based on their base sequence and other assignable properties.

During the course of their research, the scientists discovered a new type of promoter that is unique only to macrophages. The research began in the summer of 2020 as part of Gergely Nagy's OTKA grant, and the results were published in early 2024 in , a leading Q1-ranked journal in the field of biochemistry and molecular biology.

“Our findings could be published in such a prestigious journal because the regulatory element map specific to macrophages revealed a type of gene regulatory regions (promoters) specific to macrophages that had never been identified before. These promoters differ from previously described promoter types both in their composition and in their function, while their role is to ensure the characteristic gene expression pattern of a given cell type and, ultimately, the identity of the cells,” said Gergely Nagy.

Besides Gergely Nagy, there were also several members of the research group led by Professor László Nagy contributing to the research. Petros Tzerpos and Tímea Silye-Cseh participated in the earlier experiments, while Dóra Nagy-Bojcsuk assisted with carrying out the bio-informatic analyses.

“Our research belongs to the category of basic research, which means that it was not directly aimed at curing patients suffering from various diseases, yet our discovery may help us to better understand in the future what happens in certain pathological conditions. In our publication, we shared our knowledge with the scientific community about the regulatory elements that we had identified so that our results could be used in the future for therapeutic purposes and to develop new treatments,” said the researcher of the 91��Ƶ��.

The journal article also won the Count István Tisza Foundation for the 91��Ƶ�� and the 91��Ƶ�� Publication Award.

“Winning this award confirms and reaffirms that it is worth continuing our research. This recognition is particularly valuable for us because it was awarded for a discovery that is the result of so many years of intensive work,” said Gergely Nagy.

Our researchers are intent to continue their query and investigations even after the publication. While the results summarized in the recently published article were derived exclusively from untreated, resting macrophages, their current research is focused on investigating the effects of anti-inflammatory interleukin-4 on gene regulation.

Press Center - CzA