title: Large-scale global identification of protein lysine methylation in vivo.
abstract: Lysine methylation mediated by methyltransferase enzymes is present on multiple proteins throughout the cell; however, methods to uncover and characterize global protein lysine methylation patterns do not readily exist. Here we developed pan-specific methyl lysine antibodies that we utilized in immunoprecipitation experiments coupled with mass spectrometry to yield one of the first large-scale surveys of protein lysine methylation in vivo. In total, 552 different lysine methylation sites were determined, making this one of the most comprehensive global studies published to date. The large majority of these sites have not been yet reported. These sites showed significantly enriched sequence motifs and resided in proteins that are involved in diverse biological processes, particularly in chromatin organization. Our data provide a comprehensive view of lysine methylation in human cells and a powerful resource to facilitate investigations into the function of lysine methylation on non-histone proteins.
authors: Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, 1009C Stellar-Chance Laboratories, Philadelphia, PA, USA.
authors: Xing-Jun
authors: XJ
authors: Cao
authors: Anna M
authors: AM
authors: Arnaudo
authors: Benjamin A
authors: BA
authors: Garcia
mesh_terms: D000906:Antibodies / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000906:Antibodies; D011506:Proteins; D008239:Lysine
keywords: affinity; histone; immunoprecipitation; mass spectrometry; methylation; non-histone; proteomics
references: Nat Methods. 2005 Sep;2(9):667-75
references: 16118637
references: J Biol Chem. 2005 Feb 18;280(7):5563-70
references: 15590646
references: Nat Rev Genet. 2012 Apr 03;13(5):343-57
references: 22473383
references: Mol Cell. 2004 Apr 23;14(2):175-82
references: 15099517
references: J Biol Chem. 2008 May 30;283(22):14927-37
references: 18381279
references: Proteins. 2005 May 15;59(3):467-75
references: 15768403
references: Nature. 2004 Nov 18;432(7015):353-60
references: 15525938
references: Trends Genet. 2003 Nov;19(11):629-39
references: 14585615
references: Sci Signal. 2009 Aug 18;2(84):ra46
references: 19690332
references: Mol Cell. 2008 Feb 15;29(3):392-400
references: 18280244
references: Genes Dev. 2012 Jan 15;26(2):114-9
references: 22241783
references: J Biol Chem. 2004 Dec 17;279(51):53248-58
references: 15485804
references: Mol Cell Biol. 2007 Dec;27(24):8502-9
references: 17923702
references: Nat Cell Biol. 2002 Dec;4(12):993-7
references: 12447390
references: Curr Biol. 2002 Jan 8;12(1):1-11
references: 11790298
references: Nucleic Acids Res. 1998 Apr 15;26(8):1884-90
references: 9518480
references: Mol Cell Proteomics. 2003 Dec;2(12):1319-30
references: 14534352
references: Curr Protoc Protein Sci. 2006 Dec;Chapter 14:Unit 14.9
references: 18429299
references: Science. 2007 May 25;316(5828):1160-6
references: 17525332
references: Mutat Res. 2008 Dec 1;647(1-2):21-9
references: 18723033
references: Oncogene. 1998 Dec 24;17(25):3301-8
references: 9916992
references: Nature. 2006 Nov 30;444(7119):629-32
references: 17108971
references: Science. 2009 Aug 14;325(5942):834-40
references: 19608861
references: Curr Opin Cell Biol. 2002 Jun;14(3):286-98
references: 12067650
references: J Biol Chem. 2010 Jan 29;285(5):3341-50
references: 19940157
references: Cell. 2012 Jul 20;150(2):413-25
references: 22817900
references: Mol Cell. 2011 Oct 21;44(2):325-40
references: 21906983
references: Carcinogenesis. 2009 Jul;30(7):1139-46
references: 19423649
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D71-5
references: 22102590
references: Epigenetics Chromatin. 2011 Oct 24;4:19
references: 22024134
references: Proc Int Conf Intell Syst Mol Biol. 1997;5:147-52
references: 9322029
references: Chem Biol Drug Des. 2011 Aug;78(2):199-210
references: 21564555
references: Curr Opin Genet Dev. 2002 Apr;12(2):198-209
references: 11893494
references: Nat Biotechnol. 2005 Jan;23(1):94-101
references: 15592455
references: Nucleic Acids Res. 2007;35(21):7313-23
references: 17962312
references: Nat Chem Biol. 2008 Jun;4(6):344-6
references: 18438403
references: Bioinformatics. 2005 Aug 15;21(16):3448-9
references: 15972284
references: Mol Cell Proteomics. 2006 Jul;5(7):1314-25
references: 16627869
references: Mol Cell. 2006 Aug;23(4):607-18
references: 16916647
references: Bioinformatics. 2005 Jul 1;21(13):3049-50
references: 15817687
references: J Proteome Res. 2008 Jan;7(1):311-8
references: 18034455
references: Cell. 2006 Nov 3;127(3):635-48
references: 17081983
references: BMC Genomics. 2010 Feb 05;11:92
references: 20137074
references: Ann N Y Acad Sci. 2002 Dec;979:80-93
references: 12543719
references: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7
references: 18669648
references: Methods Mol Biol. 2007;406:89-112
references: 18287689
references: Mol Cell. 2007 Aug 17;27(4):636-46
references: 17707234
references: Cancer Res. 2012 Jul 1;72(13):3217-27
references: 22556262
references: Proteomics. 2004 Jul;4(7):1985-8
references: 15221759
references: Anal Chem. 2003 Feb 1;75(3):663-70
references: 12585499