Nrf2 Drives Epigenetic Reprogramming and Acts as the Master Regulator of KLF4 Expression and Activity in Arsenic-Induced Transformation.

ABSTRACT: Emerging evidence suggests that Nrf2 plays a pro-carcinogenic role in multiple cancers. Previous studies have shown that arsenic-induced Nrf2 activation drives metabolic reprogramming, leading to the formation of cancer stem-like cells. Here, we further demonstrate that KLF4, a key pluripotency factor, is a direct transcriptional target of Nrf2 in arsenic-treated human bronchial epithelial cells (BEAS-2B). Global chromatin immunoprecipitation sequencing (ChIP-seq) revealed multiple Nrf2 binding peaks within the KLF4 locus, overlapping with the enhancer markers H3K4me1 and H3K27Ac. Nrf2 knockout diminished KLF4 expression and reduced enhancer marker enrichment, accompanied by a global decrease in KLF4 genomic occupancy in BEAS-2B cells. Additionally, arsenic exposure enhances KLF4 binding a

SUBMITTER: Wang Z 

PROVIDER: S-EPMC12561416 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature