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Knowledge of the effects of environmental exposure to hypoxia (dissolved oxygen, DO: <2 mg/L) on critical physiological functions is essential for accurate predictions of its chronic impacts on marine communities. Epigenetic modifications involve changes in DNA (mainly DNA methylation) or surrounding chromatin, resulting in changes to the function and regulation of the gene expression but not altering the DNA sequence. Epigenetic changes permit rapid phenotypic adjustments to environmental change; increased exposure to environmental stressors could cause long-term deleterious effects on future generations, further exacerbating adverse effects on population abundance beyond those due to impaired functions in exposed species. Epigenetic modifications also play a crucial role in interactions between environmental stress and exposed species. However, little is known about the epigenetic signals occurring in aquatic invertebrates during exposure to environmental stress. In this study, the changes in global DNA methylation and regulation of the related enzyme, DNA methyltransferase (DNMT), were investigated in hepatopancreas tissues of brown shrimp (Farfantepenaeus aztecus, an important shrimp species in the Gulf of Mexico) after chronic exposure to hypoxia (DO: 1.7 mg/L for 1-2 weeks). Hypoxia exposure caused marked increases in the expression of DNMT mRNA levels in hepatopancreas tissues. In addition, 5-methylcytosine (5-mC, a methylated form of DNA base cytosine) contents were markedly increased in hepatopancreas tissues after hypoxia exposure. Collectively these results suggest that hypoxia leads to increasing in global DNA methylation through the related enzyme, DNMT, which might be involved in epigenetic modifications during exposure to environmental hypoxia in aquatic invertebrates.