TBD

Epigenetic DNA modifications are continuously formed and removed in human cells, and disruptions in the activity of DNA-binding proteins that regulate these processes can lead to cancer development. We employed a cross-disciplinary approach, combining cancer genetics, high-throughput biophysics, and nucleic acid chemistry, to conduct a comprehensive analysis of cytosine modifications in healthy individuals and AML patients across different age groups. Through novel in vitro assays, we assessed the impact of these modifications on key transcription factors involved in disease progression. Our study presents the largest repository to date of quantitative data on how DNA modifications can profoundly alter the protein-DNA binding landscape, often redirecting oncogenic transcription factors such as RUNX1 and FOXO3A to non-target sequences. We anticipate that these findings will enhance our understanding of the principles governing modification formation and pave the way for a deeper molecular insight into AML development.