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The mechanisms that underlie and dictate the different biological outcomes of E2F-1 activity have yet to be elucidated. We describe the residue-specific methylation of E2F-1 by the asymmetric dimethylating protein arginine methyltransferase 1 (PRMT1) and symmetric dimethylating PRMT5 and relate the marks to different functional consequences of E2F-1 activity. Methylation by PRMT1 hinders methylation by PRMT5, which augments E2F-1-dependent apoptosis, whereas PRMT5-dependent methylation favors proliferation by antagonizing methylation by PRMT1. The ability of E2F-1 to prompt apoptosis in DNA damaged cells coincides with enhanced PRMT1 methylation. In contrast, cyclin A binding to E2F-1 impedes PRMT1 methylation and augments PRMT5 methylation, thus ensuring that E2F-1 is locked into its cell-cycle progression mode. The Tudor domain protein p100-TSN reads the symmetric methylation mark, and binding of p100-TSN downregulates E2F-1 apoptotic activity. Our results define an exquisite level of precision in the reader-writer interplay that governs the biological outcome of E2F-1 activity.

Original publication

DOI

10.1016/j.molcel.2013.08.039

Type

Journal article

Journal

Mol Cell

Publication Date

10/10/2013

Volume

52

Pages

37 - 51

Keywords

Amino Acid Motifs, Apoptosis, Arginine, Cell Line, Tumor, Cell Proliferation, Chromatin Assembly and Disassembly, Cyclin A, DNA Damage, E2F1 Transcription Factor, Gene Expression Regulation, Humans, Methylation, Promoter Regions, Genetic, Protein Binding, Protein Processing, Post-Translational, Protein-Arginine N-Methyltransferases, RNA Interference, Repressor Proteins, Signal Transduction, Transcription, Genetic, Transfection