title: Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers.
abstract: Trimethyl-lysine (me3) modifications on histones are the most stable epigenetic marks and they control chromatin-mediated regulation of gene expression. Here, we determine proteins that bind these marks by high-accuracy, quantitative mass spectrometry. These chromatin "readers" are assigned to complexes by interaction proteomics of full-length BAC-GFP-tagged proteins. ChIP-Seq profiling identifies their genomic binding sites, revealing functional properties. Among the main findings, the human SAGA complex binds to H3K4me3 via a double Tudor-domain in the C terminus of Sgf29, and the PWWP domain is identified as a putative H3K36me3 binding motif. The ORC complex, including LRWD1, binds to the three most prominent transcriptional repressive lysine methylation sites. Our data reveal a highly adapted interplay between chromatin marks and their associated protein complexes. Reading specific trimethyl-lysine sites by specialized complexes appears to be a widespread mechanism to mediate gene expression.
authors.affiliation: Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany. m.vermeulen-3@umcutrecht.nl
authors.forename: Michiel
authors.initials: M
authors.lastname: Vermeulen
authors.forename: H Christian
authors.initials: HC
authors.lastname: Eberl
authors.forename: Filomena
authors.initials: F
authors.lastname: Matarese
authors.forename: Hendrik
authors.initials: H
authors.lastname: Marks
authors.forename: Sergei
authors.initials: S
authors.lastname: Denissov
authors.forename: Falk
authors.initials: F
authors.lastname: Butter
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Lee
authors.forename: Jesper V
authors.initials: JV
authors.lastname: Olsen
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Hyman
authors.forename: Henk G
authors.initials: HG
authors.lastname: Stunnenberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism; D042421:Histone Code; D006801:Humans; D008239:Lysine / Q000378:metabolism; D013058:Mass Spectrometry; D008745:Methylation; D040901:Proteomics / Q000379:methods
chemical_list: D002843:Chromatin; D051548:Histone Acetyltransferases; D008239:Lysine