mESC histone modifications under normoxia and hypoxia
The physiological behavior of mouse embryonic stem cells (mESCs) is intricately regulated by microenvironmental oxygen levels, with normoxia (21% O2) and hypoxia (1-5% O2) exhibiting distinct impacts on self-renewal, differentiation, and metabolic adaptation. However, the epigenetic mechanisms underlying oxygen-dependent gene expression remain poorly characterized. This study investigates the dynamic alterations of histone modifications associated with transcriptional regulation—specifically, the active promoter mark H3K4me3 (trimethylation of histone H3 lysine 4) and the enhancer mark H3K27ac (acetylation of histone H3 lysine 27)—in mESCs under normoxic versus hypoxic conditions. Utilizing chromatin immunoprecipitation followed by sequencing (ChIP-seq), we systematically mapped genome-wide occupancy patterns of H3K4me3 and H3K27ac, identifying oxygen-sensitive epigenetic landscapes that correlate with differential gene activity. Comparative analysis revealed hypoxia-induced redistribution of these marks at loci linked to pluripotency maintenance, hypoxia-responsive pathways (e.g., HIF-1a targets), and metabolic reprogramming. These findings highlight the role of oxygen tension in reshaping the epigenetic architecture of mESCs, providing insights into how microenvironmental cues fine-tune stem cell functionality through histone modification dynamics. This work advances our understanding of epigenetic plasticity in stem cells and may inform strategies for optimizing in vitro culture conditions or manipulating cell fate under physiological or pathological oxygen gradients. Overall design: ChIP-seq of the histone modifications H3K4me3 and H3K27ac in mESCs under normoxia and hypoxia, respectively