Function
Polycomb group (PcG) that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex. Involved in DNA damage response and is recruited at double-strand breaks (DSBs). Acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting the PRC2 complex: it is however unclear whether recruitment of the PRC2 complex to H3K36me3 leads to enhance or inhibit H3K27me3 methylation mediated by the PRC2 complex. According to some reports, PRC2 recruitment by PHF1 promotes H3K27me3 and subsequent gene silencing by inducing spreading of PRC2 and H3K27me3 into H3K36me3 loci. According to another report, PHF1 recruits the PRC2 complex at double-strand breaks (DSBs) and inhibits the activity of PRC2. Regulates p53/TP53 stability and prolonges its turnover: may act by specifically binding to a methylated from of p53/TP53.
Gene References into Functions
- the increase of DNA accessibility within the H3K36me3-containing nucleosome, instigated by the Tudor domain of PHF1 binding to H3K36me3, is dramatically enhanced by the PHF1 N-terminal domain. PMID: 28082396
- ZC3H7B-BCOR and MEAF6-PHF1 fusions occurred predominantly in S100 protein-negative and malignant ossifying fibromyxoid tumors. PMID: 24285434
- the F61L/S86F mutant of MTF2 Tudor-PHD1 was able to bind to H3K36me3 as strong as the PHF1 Tudor bound to this PTM . We concluded that the hydrophobic patch plays an essential role in binding of these Tudors to methylated chromatin PMID: 25923537
- PCL1 binds to and stabilizes p53 to induce cellular quiescence PMID: 26494712
- full-length PHF1 in HEK293 cells co-localizes with histone K27me3, but not with K36me3, and this co-localization depends on the trimethyllysine binding pocket indicating that K27me3 is an in vivo target for the PHF1 Tudor domain PMID: 23954330
- present two more ESS with MEAF6/PHF1 detected by transcriptome sequencing (case 1) and RT-PCR (case 2), proving that this fusion is recurrent in ESS PMID: 24530230
- ZC3H7B-BCOR and MEAF6-PHF1 fusions occurred predominantly in S100 protein-negative and malignant OFMT. PMID: 24285434
- Underscore the likely importance of PHF1 rearrangements in the pathogenesis of ossifying fibromyxoid tumors of soft parts. PMID: 23887158
- PHF1b may be a molecular transducer of GABA A receptor function and thus GABA-mediated neurotransmission in the central nervous system. PMID: 23879974
- Morphological features, immunoprofile and fluorescence in situ hybridization rearrangements of JAZF1 and PHF1 genes were correlated with tumor category and outcome in endometrial sarcomas PMID: 22918161
- The histone H3K36me3 binding by the Tudor domains of PHF1, PHF19 and likely MTF2 provide another recruitment and regulatory mechanism for the PRC2 complex. PMID: 23228662
- All endometrial stromal sarcomas showing sex cords had PHF1 genetic rearrangement, suggesting that such rearrangements may induce sex cord differentiation. PMID: 23211293
- Polycomb group protein PHF1 regulates p53-dependent cell growth arrest and apoptosis PMID: 23150668
- findings suggest that PHF1 can mediate deposition of the repressive H3K27me3 mark and acts as a cofactor in early DNA-damage response PMID: 23142980
- findings show that the interaction of Phf19 with H3K36me2 and H3K36me3 is essential for PRC2 complex activity and for proper regulation of gene repression in embryonic stem cells PMID: 23104054
- The PHF1 gene, previously shown to be the 3'-partner of fusion genes in endometrial stromal tumors, is also recurrently involved in the pathogenesis of ossifying fibromyxoid tumors. PMID: 22796436
- The role of PHF1 in H3K27 methylation and Hox gene silencing is reported. PMID: 18086877
- PHF1 modulates the activity of Ezh2 in favor of the repressive H3K27me3 mark PMID: 18285464
- PHF1 interacts physically with Ku70/Ku80, suggesting that PHF1 promotes nonhomologous end-joining processes. PMID: 18385154
- predicted 684-amino acid JAZF1/PHF1 chimeric protein retained one zinc finger domain from JAZF1 and the two zinc finger domains from PHF1, and its oncogenic mechanism should be similar to that of the JAZF1/SUZ12 protein PMID: 18722875
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Involvement in disease
A chromosomal aberration involving PHF1 may be a cause of endometrial stromal tumors. Translocation t(6;7)(p21;p22) with JAZF1. Translocation t(1;6)(p34;p21) with MEAF6.
Subcellular Location
Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Localizes specifically to the promoters of numerous target genes. Localizes to double-strand breaks (DSBs) sites following DNA damage. Co-localizes with NEK6 in the centrosome.
Protein Families
Polycomblike family
Tissue Specificity
Highest levels in heart, skeletal muscle, and pancreas, lower levels in brain, placenta, lung, liver and kidney.
