Comparative Proteomic Analysis of Histone Modifications upon Acridone Derivative 8a-Induced CCRF-CEM Cells by Data Independent Acquisition

The lead compound acridone derivative 8a showed potent anti-proliferative activity by inducing DNA damage through direct stacking with DNA bases and triggering ROS in CCRF-CEM cells. To define the chromatin alterations during DNA damage sensing and repair, a detailed quantitative map of single and co-existing histone post-translational modifications (PTMs) in CCRF-CEM cells affected by 8a was performed by Data Independent Acquisition (DIA) method on QE-plus. A total of 79 distinct and 164 co-existing histone PTMs were quantified, of which 16 distinct histone PTMs exhibited significantly altered when comparing 8a-treated cells with vehicle control cells. The changes in histone PTMs were confirmed by western blotting analysis for four H3 and one H4 histone markers. The up-regulated di-methylation on H3K9, H3K36 and H4K20 implied that CCRF-CEM cells might accelerate DNA damage repair in order to counteract the DNA lesion induced by 8a, which was verified by an increment in the 53BP1 foci localization at the ...