Unravelling the regulatory network underlying divergent expression of the key lipid metabolism transcription factor SREBP in two congeneric oyster species.

SREBP serves as the master transcriptional regulator of lipid metabolism, playing a crucial role in temperature adaptation. However, the regulatory mechanisms controlling SREBP expression remain poorly understood in marine organisms. The basic bHLH domain of single-copy SREBP was highly conserved in mollusks, confirming its fundamental role in lipid metabolic regulation. We observed significantly higher SREBP gene expression in the relatively cold-adapted Crassostrea gigas compared to the warm-adapted Crassostrea angulata. The large and stably inherited deletion in the SREBP promoter region of C. gigas prevented binding of repressive transcription factor POU4F3, partially explaining its higher expression levels. Additionally, the eGWAS analysis identified 119 candidate genes potentially associated with SREBP expression regulation. The direct interaction of SREBP with PPP6C and the non-binding PRP4 may activate downstream regulatory pathways of SREBP through phosphorylation mechanisms. The higher expressed activating transcription factor PRRX2 in C. gigas could simultaneously activate the promoter activity in both oyster species, potentially explaining the elevated expression of SREBP in C. gigas. This study provided the first comprehensive characterization the regulatory network of SREBP expression in marine organisms, providing new insights into lipid metabolism for temperature adaptation in the context of global warming.