Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
---|---|
Journal | Cell |
Volume | 142 |
Issue number | 6 |
Pages (from-to) | 967-80 |
Number of pages | 14 |
ISSN | 0092-8674 |
DOIs | |
Publication status | Published - 17 Sep 2010 |
- Chromatin, Epigenesis, Genetic, Gene Expression Regulation, Genome-Wide Association Study, Hela Cells, Histone Acetyltransferases, Histone Code, Humans, Lysine, Mass Spectrometry, Methylation, Proteomics
Research areas
ID: 32355662