GSE133336
Reversible 5-formyluracil DNA-histone crosslinks: formation and biological effects
5-Formyluracil (5fU) is a vital DNA modification that widely presents in cells and organisms. A unique feature of 5fU is the presence of a potentially reactive aldehyde group in its structure, which can realize addition and condensation reactions. However, the biological function details of 5fU are still largely elusive; especially the relationship with protein is still unclear. Herein, we have first showed that 5fU bases have strong affinity with proteins and can yield reversible DNA-protein conjugates with nuclear proteins even under certain spatial space. Besides, 5fU can influence physical properties of nucleosome even chromatin by increasing nucleosome occupancy and stability. What's more, we firstly confirmed the existence of 5fU-histone crosslinking in thyroid carcinoma tissue by the CHIP of histone H4 combined with LC-MS. These results suggesting the DNA-protein crosslinks (DPC) formation between 5fU and nucleosome core particles may play a potential role in vivo, such as influencing DNA transactions, altering chromatin structure, and stabilizing the nucleosome. In addition, the Schiff base resulted by 5fU may provide us a new direction for capture even quantification of this modification nucleobase based on this condensation reaction with proteins for further epigenetic studies. Overall design: PAGE, LC-MS, next-generation sequencing were applied to detect the interaction between 5fU and histones.