title: A chemical proteomics approach for global analysis of lysine monomethylome profiling.
abstract: Methylation of lysine residues on histone proteins is known to play an important role in chromatin structure and function. However, non-histone protein substrates of this modification remain largely unknown. An effective approach for system-wide analysis of protein lysine methylation, particularly lysine monomethylation, is lacking. Here we describe a chemical proteomics approach for global screening for monomethyllysine substrates, involving chemical propionylation of monomethylated lysine, affinity enrichment of the modified monomethylated peptides, and HPLC/MS/MS analysis. Using this approach, we identified with high confidence 446 lysine monomethylation sites in 398 proteins, including three previously unknown histone monomethylation marks, representing the largest data set of protein lysine monomethylation described to date. Our data not only confirms previously discovered lysine methylation substrates in the nucleus and spliceosome, but also reveals new substrates associated with diverse biological processes. This method hence offers a powerful approach for dynamic study of protein lysine monomethylation under diverse cellular conditions and in human diseases.
authors.affiliation: From the ‡The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P.R. China;
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Wu
authors.affiliation: §Jingjie PTM BioLab (Hangzhou) Co. Ltd, Hangzhou, P.R. China;
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: From the ‡The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P.R. China;
authors.forename: Mingwei
authors.initials: M
authors.lastname: Sun
authors.affiliation: From the ‡The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P.R. China;
authors.forename: Xuelian
authors.initials: X
authors.lastname: Wan
authors.affiliation: From the ‡The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P.R. China;
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: §Jingjie PTM BioLab (Hangzhou) Co. Ltd, Hangzhou, P.R. China;
authors.forename: Tieming
authors.initials: T
authors.lastname: He
authors.affiliation: From the ‡The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P.R. China; Yingming.Zhao@uchicago.edu mjtan@simm.ac.cn.
authors.forename: Minjia
authors.initials: M
authors.lastname: Tan
authors.affiliation: From the ‡The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P.R. China; ¶Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois Yingming.Zhao@uchicago.edu mjtan@simm.ac.cn.
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000378:metabolism; D002460:Cell Line; D019295:Computational Biology; D006801:Humans; D007553:Isotope Labeling; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D000906:Antibodies; D010455:Peptides; D020543:Proteome; D008239:Lysine