Lysine Methylation Goes Global

The process of post-translational covalent modification of proteins represents a transcription-independent regulatory mechanism allowing rapid alteration of protein activity and function in response to various intra- and extracellular stimuli. Lysine methylation (KM) was deemed to be a constant covalent mark, providing long-term signaling, including the histone-dependent mechanism for transcriptonal memory. Only recently has it become apparent that lysine methylation, similar to other covalent modifications, is transient and can be dynamically regulated by an opposing activity, de-methylation. These discoveries accelerated a systematic search for other non-histone substrates of lysine methylation, especially among transcription factors. Recent findings suggest that KM affects gene expression not only at the level of chromatin, but also by modifying transcription factors.