The results of the present study showed that immediate-early gene transcription and HCMV infection of human foreskin fibroblasts (HFFs) depend on histone H3K27 trimethylation, which is under the control of EZH2, JARID2, NDY1/KDM2B and the histone demethylase JMJD3. Here, KDM6B is linked to cytomegalovirus infection.