The responsive mechanisms of DNA methylation and transcriptional regulation to acute hypoxia stress in HIF-1/VEGFA signal pathway of Japanese flounder (Paralichthys olivaceus)

Abstract

The area of marine hypoxia is gradually expanding. This phenomenon seriously affects the normal life activities of a variety of marine organisms. Japanese flounder (Paralichthys olivaceus) is an important marine economic fish. However, its responses to hypoxia are still not very clear. Here, we conducted a hypoxia treatment (2.11 ± 0.11 mg/L) on Japanese flounder. Results showed that gill tissue morphology, macroscopically, was affected significantly by the hypoxia stress, especially gill lamellas. Molecularly, the HIF-1/VEGFA signal pathway, which was related to angiogenesis, was also significantly changed. In detail, expressions of hif-1α and vegfa genes, and methylation modified levels in DNA of hif-1α gene, changed significantly. The hif-1α expressions further were correlated negatively to its methylation levels, indicating that hypoxia may affect gene expression by acting on DNA methylation. In addition, we found that the CACGCA sequence, located in −1337 and −1317 sites, was the transcription factor HIF-1 binding sequence in vegfa gene. Furthermore, the −1337 site was more important for the transcriptional regulation. Therefore, it was concluded that hypoxia affected DNA methylation, regulated transcription of related factors, induced cascade amplification in signal pathways, and then influenced physiological morphology. These findings will enrich the environmental stress knowledge, and provide a reference for the breeding of teleost fishes in hypoxia tolerance.