Quantitative Analysis of Nonhistone Lysine Methylation Sites and Lysine Demethylases in Breast Cancer Cell Lines.

Growing evidence shows that lysine methylation is a widespread protein post-translational modification (PTM) that regulates protein function on histone and nonhistone proteins. Numerous studies have demonstrated that the dysregulation of lysine methylation mediators contributes to cancer growth and chemotherapeutic resistance. While changes in histone methylation are well-documented with extensive analytical techniques available, there is a lack of high-throughput methods to reproducibly quantify changes in the abundances of the mediators of lysine methylation and nonhistone lysine methylation (Kme) simultaneously across multiple samples.

Quantitative analysis of non-histone lysine methylation sites and lysine demethylases in breast cancer cell lines.

Growing evidence shows that lysine methylation is a widespread protein post-translational modification that regulates protein function on histone and non-histone proteins. Numerous studies have demonstrated that dysregulation of lysine methylation mediators contributes to cancer growth and chemotherapeutic resistance. While changes in histone methylation are well documented with extensive analytical techniques available, there is a lack of high-throughput methods to reproducibly quantify changes in the abundances of the mediators of lysine methylation and non-histone lysine methylation (Kme) simultaneously across multiple samples.

Identification of nonhistone substrates of the lysine methyltransferase PRDM9.

Lysine methylation is a dynamic, posttranslational mark that regulates the function of histone and nonhistone proteins. Many of the enzymes that mediate lysine methylation, known as lysine methyltransferases (KMTs), were originally identified to modify histone proteins but have also been discovered to methylate nonhistone proteins. In this work, we investigate the substrate selectivity of the KMT PRDM9 to identify both potential histone and nonhistone substrates.

Global lysine methylome profiling using systematically characterized affinity reagents.

Lysine methylation modulates the function of histone and non-histone proteins, and the enzymes that add or remove lysine methylation-lysine methyltransferases (KMTs) and lysine demethylases (KDMs), respectively-are frequently mutated and dysregulated in human diseases. Identification of lysine methylation sites proteome-wide has been a critical barrier to identifying the non-histone substrates of KMTs and KDMs and for studying functions of non-histone lysine methylation. Detection of lysine methylation by mass spectrometry (MS) typically relies on the enrichment of methylated peptides by pan-methyllysine antibodies.