In conclusion, this study confirms not only the co-presence of two epigenetic modification mechanisms–DNA methylation and H3K27me3–in a newborn rat model of hyperoxia-induced BPD, but also the joint contribution of DNMT3b-mediated DNA methylation and EZH2-mediated H3K27me3 to RUNX3 protein down-regulation in the late stages of BPD. This evidence concerns the gene RUNX3 and bronchopulmonary dysplasia.