Dynamic methylation pattern of cyp19a1a core promoter during zebrafish ovarian folliculogenesis

Abstract

In vertebrates, the aromatase coded by the cyp19a1a gene can catalyze the conversion from androgens to estrogens. Thus, the regulatory mechanisms of cyp19a1a gene expression are a critical research field in reproductive endocrinology. In this study, we use zebrafish as a model to study the dynamic methylation levels of the cyp19a1a gene core promoter during zebrafish ovarian folliculogenesis. The results show that there is an apparent fluctuation of the methylation levels of zebrafish cyp19a1a core promoter. Moreover, the methylation levels are inversely correlated with the expression levels of cyp19a1a transcripts when the ovarian follicles develop from PV into the MV stage. Also, the CpG dinucleotides which are close to the transcriptional starting site may have provided a significant blocking effect on inhibiting the transcriptional function of RNA polymerase II. Taken together, the results from the present study strongly suggest that DNA methylation was one of mechanisms that are involved in the regulation of cyp19a1a gene expression during folliculogenesis. This methylation mechanism modifying transcriptional process accompanied with zebrafish ovarian folliculogenesis might also shed new light on the regulation of cyp19a1a expression during the ovarian developmental stage in other vertebrates.

DNA Methylation Inhibits the Expression of CFSH in Mud Crab

“…After transfection, 10 positive clones were selected and sequenced. The analysis was performed as previously described (17). The rate of promoter methylation was calculated by the formula I Me /10, where I Me and 10 represent the number of the methylated promoters and sequenced promoters, respectively.…”

“…CpG island is the major target for methylation and plays a vital role in inhibiting gene expression (16). Dynamic methylation pattern of CpG island in a core promoter is involved in the regulation of gene expression (17). In insects, DNA methylation is restricted to the transcribed regions and primarily involved in behavioral plasticity and social behavior (17)(18)(19)(20)(21)(22).…”

“…Dynamic methylation pattern of CpG island in a core promoter is involved in the regulation of gene expression (17). In insects, DNA methylation is restricted to the transcribed regions and primarily involved in behavioral plasticity and social behavior (17)(18)(19)(20)(21)(22). Unlike mammals and insects, studies on DNA methylation are relatively rare in crustaceans and have so far been reported only in the water flea, Daphnia magna and Daphnia pulex.…”

The role of estrogens in the adipose tissue milieu

“…71,72 These promoter regions drive aromatase expression in the ovaries and bone, adipose, placental, and neuronal tissue. 81 Epigenetic regulation of aromatase by DNA methylation appears widely conserved across evolution, including in chicken, 82 rat, 83 alligator, 84 sea bass, 85 zebrafish, 86 perch, 87 eel, 88 buffalo, 89,90 sheep, and cattle. DNA methylation-the addition of a methyl group to the 5-position of cytosine-is a well-studied epigenetic mechanism, 73 and can be modulated by treatment of cells with the DNA methylation inhibitors 5-azacytidine or 2-deoxy-5-azacytidine 74 to test whether a gene is under epigenetic control.…”

“…Using this method, DNA methylation was found to regulate aromatase expression in primary APs, 75 breast adipose fibroblasts, 76 skin fibroblasts, 77 endometrial stromal cells, 78 placental choriocarcinoma, 79 placenta, 80 and neuroglia. 81 Epigenetic regulation of aromatase by DNA methylation appears widely conserved across evolution, including in chicken, 82 rat, 83 alligator, 84 sea bass, 85 zebrafish, 86 perch, 87 eel, 88 buffalo, 89,90 sheep, and cattle. 91 The mechanism by which DNA methylation regulates aromatase expression may be direct, that is, by changes at the aromatase promoter itself, 75,77 or indirect, by epigenetic alterations at unknown genomic loci.…”