Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers.
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.
Vermeulen
Michiel
M
Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany. m.vermeulen-3@umcutrecht.nl
Eberl
H Christian
HC
Matarese
Filomena
F
Marks
Hendrik
H
Denissov
Sergei
S
Butter
Falk
F
Lee
Kenneth K
KK
Olsen
Jesper V
JV
Hyman
Anthony A
AA
Stunnenberg
Henk G
HG
Mann
Matthias
M
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
D002843:Chromatin; D051548:Histone Acetyltransferases; D008239:Lysine