Transcriptional regulation of the human ferritin ... - The FASEB Journal
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Transcriptional regulation of the human ferritin ... - The FASEB Journal
block Nrf2 nuclear accumulation but inhibited Nrf2 binding to the AREs by 40% (P
The FASEB Journal • Research Communication
Transcriptional regulation of the human ferritin gene by coordinated regulation of Nrf2 and protein arginine methyltransferases PRMT1 and PRMT4 Bo-Wen Huang,* Paul D. Ray,* Kenta Iwasaki,† and Yoshiaki Tsuji*,1 *Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina, USA; and †Department of Applied Immunology, Nagoya University School of Medicine, Nagoya, Japan Antioxidant genes such as ferritin are transcriptionally activated in oxidative stress via the antioxidant responsive element (ARE), to which nuclear factor-E2-related factor 2 (Nrf2) binds and activates transcription. Histone modification plays a cooperative and essential role in transcriptional regulation; however, its role in antioxidant gene transcription remains elusive. Arsenic exposure activated ferritin transcription via the ARE concomitant with increased methylation of histones H4Arg3 (H4R3) and H3Arg17 (H3R17). To test our hypothesis that histone H4R3 and H3R17 methylation regulates ferritin transcription, H4R3 and H3R17 protein arginine (R) methyltransferases 1 and 4 (PRMT1 and PRMT4) were investigated. Arsenic exposure of human HaCaT keratinocytes induced nuclear accumulation of PRMT1 and PRMT4, histone H4R3 and H3R17 methylation proximal to the ARE, but not to the non-ARE regions of ferritin genes. PRMT1 or PRMT4 knockdown did not block Nrf2 nuclear accumulation but inhibited Nrf2 binding to the AREs by ⬃40% (P
