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| Status |
Public on Apr 27, 2010 |
| Title |
PHF8 targets histone methylation and RNA polymerase II to activate transcription |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Mutations in PHF8 are associated with X-linked mental retardationand cleft lip/cleft palate. PHF8 contains a plant homeodomain(PHD) in its N-terminus and is member of a family of JmjC-domaincontaining proteins. While PHDs can act as methyl lysine recognitionmotifs, JmjC-domains can catalyze lysine demethylation. Here,we show that PHF8 is a histone demethylase that removes repressivehistone H3 dimethyl lysine 9 marks. Our biochemical analysisrevealed specific association of the PHF8 PHD domain with histoneH3 trimethylated at lysine 4 (H3K4me3). Chromatin-immunoprecipitationfollowed by high throughput sequencing indicated that PHF8 isenriched at transcription start sites of many active or poisedgenes, mirroring the presence of RNA polymerase II (RNAPII)and of H3K4me3-bearing nucleosomes. We show that PHF8 can actas a transcriptional co-activator and its activation functionlargely depends on binding of the PHD to H3K4me3. Furthermore,we present evidence for direct interaction of PHF8 with theC-terminal domain of RNAPII. Importantly, a PHF8 disease mutantis defective in demethylation and in co-activation. This isthe first demonstration of a chromatin-modifying enzyme whichis globally recruited to promoters through its association withH3K4me3 and RNAPII.
This SuperSeries is composed of the SubSeries listed below.
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| Overall design |
Refer to individual Series
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| |
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| Contributor(s) |
Fortschegger K, Shiekhattar R |
| Citation(s) |
20421419 |
| |
| Submission date |
Mar 11, 2010 |
| Last update date |
May 15, 2019 |
| Contact name |
Klaus Fortschegger |
| Organization name |
Center for Genomic Regulation
|
| Department |
Gene Regulation
|
| Lab |
Ramin Shiekhattar
|
| Street address |
C/ Dr. Aiguader 88
|
| City |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
| |
|
| Platforms (2) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
|
| Samples (16)
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| This SuperSeries is composed of the following SubSeries: |
| GSE20563 |
Knockdown of PHF8 in HeLa S3 cells |
| GSE20725 |
ChIP-seq of PHF8 and H3K4me3 |
|
| Relations |
| BioProject |
PRJNA125037 |
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