The following is a summary of “CYP19A1 Expression Is Controlled by mRNA Stability of the Upstream Transcription Factor AP-2γ in Placental JEG3 Cells,” published in the May 2024 issue of Endocrinology by Kotomura, et al.
For a study, researchers sought to investigate the molecular mechanisms underlying the induction of CYP19A1, which encodes aromatase, during placental maturation.
Histone methylation patterns were analyzed using the JEG3 placental cytotrophoblast cell line. Cells were treated with either 3-deazaneplanocin A, an inhibitor of methyltransferases, or GSK126, a specific inhibitor of H3K27me3 methylation. Changes in CYP19A1 expression were measured, along with alterations in histone marks on the CYP19A1 promoter. Additionally, the effect of 3-deazaneplanocin A on TFAP2C expression, encoding AP-2γ, and TFAP2C mRNA stability was assessed. Adenosine methylation of TFAP2C mRNA and its impact on stability were also investigated.
Treatment with 3-deazaneplanocin A significantly increased CYP19A1 expression in JEG3 cells. This increase correlated with removing the repressive histone mark H3K27me3 from the CYP19A1 promoter. In contrast, GSK126 treatment did not induce CYP19A1 expression, indicating the specificity of H3K27me3 methylation in this process. Furthermore, 3-deazaneplanocin A treatment elevated TFAP2C expression and stabilized TFAP2C mRNA in JEG3 cells. This stabilization was associated with reduced N6-methyladenosines on TFAP2C mRNA, suggesting a role for adenosine methylation in mRNA degradation. These findings suggested that 3-deazaneplanocin A enhances AP-2γ expression by stabilizing TFAP2C mRNA, promoting CYP19A1 upregulation.
In conclusion, the study elucidated a mechanism by which 3-deazaneplanocin A promotes CYP19A1 expression through modulation of histone methylation and TFAP2C mRNA stability. The insights provided a valuable understanding of the regulatory pathways involved in placental aromatase induction, potentially informing future therapeutic strategies targeting estrogen synthesis during placental development.
Reference: academic.oup.com/endo/article-abstract/165/6/bqae055/7667233
The post 3-Deazaneplanocin A Promotes CYP19A1 Expression Through Histone Methylation and mRNA Stability Regulation During Placental Maturation first appeared on Physician's Weekly.