Methylation dictates PI.f-specific CYP19 transcription in human glial cells
Publication in refereed journal


摘要CYP19 is the single copy gene encoding for the estrogen synthetic enzyme aromatase. Alternate splicing of the promoter is the regulatory mechanism of this gene. In the brain, estrogen is synthesized in neuronal and glial cells and the gene is mainly regulated by the alternate promoter PI.f. The hormone produced in this vicinity has been associated with maintaining normal brain functions. Previously, epigenetic regulation has been shown in the promoters PII and I.3 of CYP19 in adipocytes. In the present study, the methylation of PI.f in CYP19 was examined in glial cells. Treatment of the hypomethylating agent 5-aza-2 ' deoxycytidine increased CYP19 mRNA species in U87 MG cells while little changes were observed in the other glia cell lines. As PI.f is also chiefly used in T98G cells with high expression of CYP19, the methylation statuses of the promoter in these two cell models were compared. Our results showed that treating U87 MG cells with 10 mu M 5-aza-2 ' deoxycytidine significantly induced a similar to 10-fold increase in CYP19 transcription and similar to 80% increase in aromatase activity. In contrast, the same treatment did not change either endpoint in T98G cells. Further investigation illustrated the CpGs in PI.f were differentially methylated in the two cell lines; 63% and 37% of the 14 CpG sites were methylated in U87 MG and T98G cells respectively. In conclusion, this study illustrated that the brain-specific PI.f derived CYP19 expression can be regulated by DNA methylation.
著者Tan WJ, Zhu ZP, Ye L, Leung LK
期刊名稱Molecular and Cellular Endocrinology
頁次131 - 137
關鍵詞Methylation,Aromatase,Glial cells
Web of Science 學科類別Cell Biology;Endocrinology & Metabolism;Cell Biology;Endocrinology & Metabolism

上次更新時間 2020-26-09 於 02:05