Quantitative Interaction Proteomics and Genome-wide Profiling of Epigenetic Histone Marks and Their Readers

Michiel Vermeulen, H. Christian Eberl, Filomena Matarese, Hendrik Marks, Sergei Denissov, Falk Butter, Kenneth K. Lee, Jesper V. Olsen, Anthony A. Hyman, Henk G. Stunnenberg, Matthias Mann

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

630 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)967-980
Aantal pagina's14
TijdschriftCell
Volume142
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - sep. 2010
Extern gepubliceerdJa

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