Coordinated regulation of Nrf2 and histone H3 serine 10 phosphorylation in arsenite-activated transcription of the human heme oxygenase-1 gene.

摘要: Expression of the antioxidant gene heme oxygenase-1 (HO-1) is primarily induced through NF-E2-related factor 2 (Nrf2)-mediated activation response element (ARE). Gene transcription coordinately regulated by activity at enhancer elements and epigenetic alterations such as posttranslational modification histone proteins. However, role modifications in Nrf2-ARE axis remains largely uncharacterized. The environmental contaminant arsenite a potent inducer both HO-1 expression phosphorylation H3 serine 10 (H3S10); therefore, we investigated relationships between Nrf2 H3S10 arsenite-induced, ARE-dependent, transcriptional human gene. Arsenite increased globally promoter concomitantly with HaCaT keratinocytes. Conversely, arsenite-induced were blocked N-acetylcysteine (NAC), c-Jun N-terminal kinase (JNK) inhibitor SP600125, JNK knockdown (siJNK). Interestingly, ablation SP600125 or siJNK did not inhibit nuclear accumulation nor ARE binding, despite inhibiting expression. In to arsenite, binding preceded ARE. Furthermore, arsenite-mediated occupancy phosphorylated was decreased Nrf2-deficient mouse embryonic fibroblasts. These results suggest involvement proposing that may influence additional regions. Our data highlights complex interplay arsenite-activated transcription.