To follow the Nrf2 Week #2 finding that chromatin accessibility parallels Nrf2 expression, this 2023 cell study explored how Nrf2 influences other epigenetic processes:
“We identified antioxidant response element sequences in promoter regions of genes encoding several epigenetic regulatory factors, such as histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and proteins involved in microRNA biogenesis.
- We treated cells with dimethyl fumarate (DMF), an activator of the NRF2 pathway through both the KEAP1 and GSK-3 pathways. NRF2 is able to modulate expression of HDAC1, HDAC2, HDAC3, and SIRT1 in different cell types.
- DMF treatment induced DNMT1 and DNMT3b at both mRNA and protein levels. For DNTM3a, there was a slight induction of mRNA levels but not at the protein level.
- Our data indicate that of all miRNAs analyzed, only miR-27a-3p, miR-27b-3p, miR-128-3p, and miR-155-5p associate with Nfe2l2 mRNA. NRF2 causes degradation of miR-155-5p, which is implicated in neuroinflammation and other pathologies, and is the main miRNA induced by LPS treatment in microglia. miR-155 alters expression of genes that regulate axon growth, supporting the bioinformatic prediction that miR-155 can regulate expression of genes involved in central nervous system development and neurogenesis.
Todate we only understand how epigenetic modifications affect expression and function of the NRF2 pathway. The fact that NRF2 can promote expression of type I HDACs, DNMTs, and proteins involved in miRNA biogenesis opens new perspectives on the spectrum of actions of NRF2 and its epigenetic influences.”
https://www.mdpi.com/2076-3921/12/3/641 “The Transcription Factor NRF2 Has Epigenetic Regulatory Functions Modulating HDACs, DNMTs, and miRNA Biogenesis”