27 November, 2025
researchers-uncover-mechanisms-of-dna-recognition-by-proteins

A collaborative study by researchers at Stanford University and Stockholm University has advanced the understanding of gene regulation in human cells. Published in the journal Cell on November 26, 2025, the research focuses on how proteins known as transcription factors recognize and bind to DNA, a process crucial for determining cellular functions. This discovery has significant implications for understanding various diseases, including cancer, which can arise from errors in this recognition.

Insights into KLF1 and Gene Regulation

The study zeroes in on the transcription factor KLF1, which plays a vital role in the development of red blood cells responsible for oxygen transport throughout the body. The research team employed new experimental methods to accurately measure KLF1’s interactions with DNA, both in vitro and within human cells. According to Emil Marklund, an assistant professor at Stockholm University and a participant in the study, “The most important result is that we show it is possible to understand the binding between this transcription factor and DNA in human cells, and that this behavior is consistent with what we measure in test tubes. That is an important basic science discovery.”

Understanding how KLF1 binds to DNA enhances knowledge of the broader regulatory processes that enable different cell types, such as nerve or immune cells, to express distinct gene profiles. Marklund noted that when binding is disrupted, it can lead to numerous health issues. Research indicates that over half of all mutations linked to genetic traits occur in regions of DNA where transcription factors, like KLF1, bind.

Broader Implications and Future Research Directions

Ph.D. student Julia M. Schaepe, the study’s first author, highlighted the broader implications of their findings. She stated, “We discovered that this transcription factor pays attention to much more of the DNA sequence surrounding its binding sites than previously thought.” By integrating precise measurements from both laboratory settings and human cells with physical models, the researchers were able to form a more comprehensive understanding of DNA recognition and gene regulation.

These insights not only advance fundamental science but also pave the way for future research into gene regulation mechanisms, which could significantly impact therapeutic approaches for various diseases. The study exemplifies the potential of interdisciplinary collaboration in enhancing scientific knowledge and fostering innovative solutions to complex biological challenges.

For further information, refer to the original study: Julia M. Schaepe et al, “Thermodynamic principles link in vitro transcription factor affinities to single-molecule chromatin states in cells,” published in Cell (2025). DOI: 10.1016/j.cell.2025.11.008.