Ctnnb1 and Keap1-Nrf2 mediating divergent heat resistance in two congeneric oysters

Global warming has led to rising temperatures of sea, which in turn increases oxidative stress on marine organisms. The Nuclear factor erythroid 2-related factor 2 (Nrf2), as widely recognized antioxidative transcription factor, has been reported playing a significant role in the thermal stress response of marine organisms; however, its precise function and regulatory mechanisms remain unclear. In this study, we demonstrated regulatory mechanisms of Nrf2 in two congeneric oyster species with differential thermal tolerance Crassostrea gigas (C. gigas) and Crassostrea angulata (C. angulata). Firstly, we confirmed that Nrf2 can activate the expression of antioxidant (including Ggt1, Segpx) and immune-related genes (including Cebpg), while inhibiting the expression of pro-oxidant genes (including Cyp13B1). Moreover, the upstream regulatory factors (Ctnnb1 and Keap1), acting as temperature sensors, modulate the expression abundance of Nrf2 in oysters at transcriptional and post-translational levels to mitigate heat-induced oxidative stress. And their differential expression patterns are involved in shaping higher antioxidant capacity and thermal tolerance in C. angulata. This study firstly characterized the Nrf2 gene function and its regulatory network (Ctnnb1 and Keap1-Nrf2) in marine organisms, providing new insights for assessing the adaptive potential heat tolerance of oysters and other marine species facing the threat of global warming.