This study emphasizes the interplay between DNA methylation and H3K27me3 in a rat model of hyperoxia-induced BPD, highlighting the combined effects of DNMT3b-mediated DNA methylation and EZH2-mediated H3K27me3 on the downregulation of RUNX3 protein during the later stages of BPD. Here, RUNX3 is linked to bronchopulmonary dysplasia.