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Epstein-Barr virus (EBV) causes human lymphoid malignancies and epithelial carcinomas including nasopharyngeal carcinoma (NPC),and the EBV product latent membrane protein 1 (LMP1) has been identified as an oncogene.EBV can epigenetically reprogram some lymphocyte processes,including cell immortalization.However,the host-cell interplay by LMP1 remains largely unknown.We have discovered here that LMP1 silences the Hox gene signature in both cells and biopsies.The stalling of RNA polymerase Ⅱ (Pol Ⅱ) was initiated by LMP1 at Hox genes,whereas irradiation reactivated the stalled Hox genes by releasing stalled Pol Ⅱ.TET3,but not TET2 or TET1,contributes to the stalling of Hox genes on 5hmC in a DNA demethylation-dependcnt manner.Furthermore,we found that HoxC8,one of the genes stalled by LMP1,not only inhibited tumor growth but also up-regulated tricarboxylic acid (TCA) cycle-related genes as a repressor of the Warburg effect.Accordingly,we propose that the heightened suppressive activity of stalled genes activates oncogenic activity via viral latency products that induce metabolic reprogramming.