Objective：Accumulation of reactive oxygen species（ROS） in skeletal muscle cells promotes apoptosis，which represents a key mechanism underlying the loss of muscle mass during aging. Previously we have demonstrated that the transcription factor E2F1 promotes the transcription of the pro-apoptotic gene PERP in skeletal muscle cells（C2C12）. In the present stuy we investigated the epigenetic mechanism whereby E2F1 expression is stimulated by ROS in C2C12 cells. Methods：Real-time qPCR and Western blotting were used to examine gene expression levels. Chromatin immunoprecipitation was used to determine the interaction between protein and DNA. Results：We report that E2F1 levels were up-regulated in C2C12 exposed to H2O2. Up-regulation of E2F1 expression by H2O2 treatment was accompanied by erasure of dimethyl H3K9 from the E2F1 promoter. Further study revealed that H2O2 treatment promoted the binding of KDM3A，a histone demethylase，on the E2F1 promoter. In contrast，KDM3A depletion by siRNA significantly dampened the induction of E2F1 expression by H2O2 treatment. Concomitantly，KDM3A knockdown decreased the levels of acetylated H3 and trimethylated H3K4 but restored the levels of dimethylated H3K9 on the E2F1 promoter. Conclusion：Our data suggest that KDM3A may participate in H2O2 treatment-induced E2F1 trans-activation by modulating histone modifications on the E2F1 promoter.