title: Large scale analysis of co-existing post-translational modifications in histone tails reveals global fine structure of cross-talk.
abstract: Mass spectrometry (MS) is a powerful analytical method for the identification and quantification of co-existing post-translational modifications in histone proteins. One of the most important challenges in current chromatin biology is to characterize the relationships between co-existing histone marks, the order and hierarchy of their deposition, and their distinct biological functions. We developed the database CrossTalkDB to organize observed and reported co-existing histone marks as revealed by MS experiments of histone proteins and their derived peptides. Statistical assessment revealed sample-specific patterns for the co-frequency of histone post-translational modifications. We implemented a new method to identify positive and negative interplay between pairs of methylation and acetylation marks in proteins. Many of the detected features were conserved between different cell types or exist across species, thereby revealing general rules for cross-talk between histone marks. The observed features are in accordance with previously reported examples of cross-talk. We observed novel types of interplay among acetylated residues, revealing positive cross-talk between nearby acetylated sites but negative cross-talk for distant ones, and for discrete methylation states at Lys-9, Lys-27, and Lys-36 of histone H3, suggesting a more differentiated functional role of methylation beyond the general expectation of enhanced activity at higher methylation states.
authors.affiliation: From the Department of Biochemistry and Molecular Biology University of Southern Denmark Campusvej 55 DK-5230 Odense M, Denmark veitveit@bmb.sdu.dk.
authors.forename: Veit
authors.initials: V
authors.lastname: Schwämmle
authors.affiliation: From the Department of Biochemistry and Molecular Biology University of Southern Denmark Campusvej 55 DK-5230 Odense M, Denmark.
authors.forename: Claudia-Maria
authors.initials: CM
authors.lastname: Aspalter
authors.affiliation: From the Department of Biochemistry and Molecular Biology University of Southern Denmark Campusvej 55 DK-5230 Odense M, Denmark.
authors.forename: Simone
authors.initials: S
authors.lastname: Sidoli
authors.affiliation: From the Department of Biochemistry and Molecular Biology University of Southern Denmark Campusvej 55 DK-5230 Odense M, Denmark.
authors.forename: Ole N
authors.initials: ON
authors.lastname: Jensen
mesh_terms: D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D030562:Databases, Protein; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D020407:Internet; D013058:Mass Spectrometry; D008745:Methylation; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D020239:Receptor Cross-Talk / Q000502:physiology*
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes
references.citation: PLoS Genet. 2007 Mar 2;3(3):e38
references.pmid: 17335352
references.citation: Nat Genet. 2008 Jul;40(7):897-903
references.pmid: 18552846
references.citation: J Biol Chem. 2002 Apr 5;277(14):11621-4
references.pmid: 11850414
references.citation: Genetics. 2003 Sep;165(1):115-25
references.pmid: 14504221
references.citation: Nat Rev Mol Cell Biol. 2006 Jun;7(6):391-403
references.pmid: 16723975
references.citation: Cell. 2006 Apr 21;125(2):315-26
references.pmid: 16630819
references.citation: J Biol Chem. 2007 Feb 16;282(7):4408-4416
references.pmid: 17166833
references.citation: J Biol Chem. 2011 Mar 11;286(10):7983-7989
references.pmid: 21239496
references.citation: Cell. 2007 May 18;129(4):823-37
references.pmid: 17512414
references.citation: Mol Cell. 2012 Jul 27;47(2):203-14
references.pmid: 22795131
references.citation: Proteomics. 2004 Jun;4(6):1534-6
references.pmid: 15174123
references.citation: Database (Oxford). 2011 Mar 29;2011:bar009
references.pmid: 21447597
references.citation: Nature. 2000 Jan 6;403(6765):41-5
references.pmid: 10638745
references.citation: Bioinformatics. 2004 Jun 12;20(9):1466-7
references.pmid: 14976030
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2086-91
references.pmid: 17284592
references.citation: Mol Cell Proteomics. 2010 May;9(5):838-50
references.pmid: 20150217
references.citation: Anal Chem. 2013 Sep 3;85(17):8232-9
references.pmid: 23889513
references.citation: Expert Rev Proteomics. 2007 Aug;4(4):491-503
references.pmid: 17705707
references.citation: J Am Chem Soc. 2004 Mar 24;126(11):3386-7
references.pmid: 15025441
references.citation: Proteomics. 2004 Jan;4(1):1-10
references.pmid: 14730666
references.citation: Science. 2001 Aug 10;293(5532):1074-80
references.pmid: 11498575
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D337-42
references.pmid: 22140112
references.citation: J Biol Chem. 2008 Nov 28;283(48):33585-90
references.pmid: 18835819
references.citation: Electrophoresis. 1999 Dec;20(18):3551-67
references.pmid: 10612281
references.citation: J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89
references.pmid: 24226387
references.citation: Mol Cell Proteomics. 2009 Oct;8(10):2266-84
references.pmid: 19654425
references.citation: Nat Rev Genet. 2009 Oct;10(10):669-80
references.pmid: 19736561
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2926-31
references.pmid: 20133639
references.citation: Nature. 2011 Jan 20;469(7330):343-9
references.pmid: 21248841
references.citation: Genes Dev. 2002 Feb 15;16(4):479-89
references.pmid: 11850410
references.citation: BMC Genomics. 2012 Jul 03;13:301
references.pmid: 22759587
references.citation: Mol Cell. 2004 Nov 5;16(3):453-63
references.pmid: 15525517
references.citation: Anal Biochem. 2002 Jul 15;306(2):259-69
references.pmid: 12123664
references.citation: J Proteomics. 2012 Jun 27;75(12):3419-33
references.pmid: 22234360
references.citation: Mol Cell Proteomics. 2006 Jul;5(7):1314-25
references.pmid: 16627869
references.citation: Nat Struct Mol Biol. 2005 Feb;12(2):110-2
references.pmid: 15702071
references.citation: Mol Cell. 2007 Dec 14;28(5):730-8
references.pmid: 18082598
references.citation: Cell. 2010 Oct 15;143(2):212-24
references.pmid: 20888037
references.citation: PLoS Biol. 2005 Oct;3(10):e328
references.pmid: 16122352
references.citation: EMBO J. 2004 Oct 13;23(20):4061-71
references.pmid: 15385962
references.citation: J Cell Biochem. 2004 Jul 1;92(4):691-700
references.pmid: 15211567