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| Status |
Public on Oct 16, 2012 |
| Title |
Phf19 links methylated lysine 36 of histone H3 to regulation of Polycomb activity [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Polycomb group proteins are transcriptional repressors that play essential roles in regulating genes required for differentiation and embryonic development. The Polycomb repressive complex 2 (PRC2) contains the methyltransferase activity for lysine 27 on histone 3 (H3K27me3), which is a docking site for the PRC1 complex and leads to gene repression. However, the role of other histone modifications in regulating PRC2 activity is just beginning to be understood. Here we show that direct recognition of histone H3 methylated at lysine 36 (H3K36me), an mark associated with activation, by the PRC2 subunit Phf19 is required for the full enzymatic activity of the PRC2 complex. We provide structural evidence for this interaction by nuclear magnetic resonance spectroscopy (NMR). Using genome-wide chromatin binding analyses and expression analyses, we show that Phf19 binds to a subset of PRC2 targets in embryonic stem (ES) cells, and that this is required for their repression and for H3K27me3 deposition. These findings reveal that the H3K36me2/3-Phf19 interaction is essential for PRC2 complex activity and for proper regulation of gene repression in ES cells.
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| Overall design |
We determined the genome binding/occupancy profile of Phf19, H3K36me3, H3K36me2, H3K27me3 and Suz12 by high throughput sequencing in mouse embryonic stem cells. For Phf19 two independent biological replicas were performed and Phf19 binding sites were defined as those sites (ChIP-seq peaks) present in both replicas. H3K27me3 was evaluated in control ES cells and cells depleted of Phf19 (shRd and shPhf19 respectively).
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| Contributor(s) |
Di Croce L, Ballare C, Morey L, Cozzuto L, Lange M |
| Citation(s) |
23104054 |
| |
| Submission date |
Oct 15, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Luciano Di Croce |
| E-mail(s) |
[email protected]
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| Phone |
+34933160132
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| Organization name |
Centre for Genomic Regulation
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| Street address |
Dr. Aiguader, 88
|
| City |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA177615 |
| SRA |
SRP016121 |
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