PHF1

This gene encodes a Polycomb group protein. The protein is a component of a histone H3 lysine-27 (H3K27)-specific methyltransferase complex, and functions in transcriptional repression of homeotic genes. The protein is also recruited to double-strand breaks, and reduced protein levels results in X-ray sensitivity and increased homologous recombination. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq]

Full Name

PHD finger protein 1

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 and 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.

Biological Process

Cellular response to DNA damage stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Chromatin organizationManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of histone H3-K27 methylationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of histone H3-K27 methylationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

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.

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.