摘要：SummaryThe progesterone receptor (PR) is an inducible transcription factor that plays critical roles in female reproductive processes and in several aspects of breast cancer tumorigenesis. Our report describes the type I protein arginine methyltransferase 1 (PRMT1) as a cofactor controlling progesterone pathway, through the direct methylation of PR. Mechanistic assays in breast cancer cells indicate that PRMT1 methylates PR at the arginine 637 and reduces the stability of the receptor, thereby accelerating its recycling and finally its transcriptional activity. Depletion of PRMT1 decreases the expression of a subset of progesterone-inducible genes, controlling breast cancer cells proliferation and migration. Consistently, Kaplan-Meier analysis revealed that low expression of PRMT1 predicts a longer survival among the subgroup with high PR. Our study highlights PR methylation as a molecular switch adapting the transcription requirement of breast cells during tumorigenesis.Graphical AbstractDisplay OmittedHighlights•The progesterone receptor (PR) is methylated by PRMT1 upon progestin treatment•PRMT1-dependent methylation controls the stability of PR•PRMT1 activates genes involved in the regulation of cell migration and invasion•PRMT1 expression influences the survival of patients with PR-positive breast cancerMolecular Biology; Molecular Mechanism of Gene Regulation; Molecular Interaction; Cancer
