PHF1
Domain
The Tudor domain recognizes and binds H3K36me3 (PubMed:23142980, PubMed:23228662, PubMed:23273982).
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 (PubMed:18285464, PubMed:23273982). According to another report, PHF1 recruits the PRC2 complex at double-strand breaks (DSBs) and inhibits the activity of PRC2 (PubMed:23142980). Regulates p53/TP53 stability and prolonges its turnover: may act by specifically binding to a methylated from of p53/TP53.
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.
Sequence Similarities
Belongs to the Polycomblike family.
Tissue Specificity
Highest levels in heart, skeletal muscle, and pancreas, lower levels in brain, placenta, lung, liver and kidney.
Cellular localization
- Nucleus
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- 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.
Alternative names
PCL1, PHF1, PHD finger protein 1, Protein PHF1, hPHF1, Polycomb-like protein 1, hPCl1