Hyperoxia Induced Chromatin Remodeling in Mesenchymal Stromal Cells

Chromatin is a highly dynamic entity of the eukaryotic cell nucleus. New evidences are emerging with a support of the notion that chromatin can locally and globally rearrange itself to adapt with the cellular microenvironmental changes. Such changes include oxidative stress such as supraphysiological oxygen level, found in hyperoxia. Although it is known that hyperoxia can cause DNA damage and alterations in cell function, it is not well understood how the chromatin architecture changes under such condition and what is the functional significance of such change. Characterization and quantification of chromatin remodeling is therefore a first step to understand the chromatin dynamics for understanding complex subnuclear behavior under single or multiple environmental stresses. Towards that end, in this work, human bone marrow derived mesenchymal stromal cells were used to characterize such chromatin level alterations under the changing oxidative stress on cells. Hyperoxia was applied using hydrogen peroxide treatment. Chromatin remodeling was hindered by the inhibition of methyltransferase EZH2, which regulates ARID1A activity and chromatin compaction. Epigenetic modifications and DNA damage under hyperoxia was investigated, which was found affected by the pharmacological inhibition of chromatin remodeling. The developed techniques and findings might provide us with new mechanism and intervention strategies to target genotoxic hyper-oxidative stress, which is common in degenerative diseases and aging, and also for cell therapy in regenerative medicine. ### Competing Interest Statement The authors have declared no competing interest.