PHF8 : PHD finger protein 8
Description
The PHF8 (PHD finger protein 8) is a protein-coding gene located on chromosome X.
The PHF8 gene provides instructions for making a protein that is found in the cell nucleus, particularly in brain cells before and just after birth. The PHF8 protein is part of a group known as zinc finger proteins, which contain one or more short regions called zinc finger domains. These regions include a specific pattern of protein building blocks (amino acids) and one or more charged atoms of zinc (zinc ions). The folded configuration of the zinc finger domain stabilizes the protein and allows it to attach (bind) to other molecules.The PHF8 protein contains a specific zinc finger domain called a PHD domain, which binds to complexes called chromatin, the network of DNA and proteins (called histones) that packages DNA into chromosomes. Binding with the PHF8 protein is part of the process that changes the structure of chromatin (chromatin remodeling) to alter how tightly regions of DNA are packaged. Chromatin remodeling is one way gene activity (expression) is regulated; when DNA is tightly packed genes tend to be turned off, compared to when DNA is loosely packed and genes are usually turned on. While the PHF8 protein is bound to chromatin, another domain of the PHF8 protein, called Jumonji C (JmjC), removes molecules called methyl groups from histones. Removing these methyl groups (demethylation) causes the chromatin to become loosely packed and increases the expression of specific genes.
PHF8 is a histone lysine demethylase that specifically removes di- and monomethyl groups from histone H3 lysine 9 (H3K9Me1 and H3K9Me2), histone H3 lysine 27 (H3K27Me2), and histone H4 lysine 20 (H4K20Me1). This demethylation activity acts as a transcriptional activator, as the modified residues are typically associated with gene repression. PHF8 plays a critical role in cell cycle progression, particularly in regulating the transition from G1 to S phase. It also acts as a coactivator of ribosomal DNA (rDNA) transcription, stimulating the production of ribosomal RNA by polymerase I. Additionally, PHF8 is essential for brain development, likely by regulating the expression of neuron-specific genes. The enzyme's activity towards H4K20Me1 is specific to nucleosomes and is absent when only histone octamers are used as substrates. PHF8 may also weakly demethylate H3K36Me2, but the physiological relevance of this activity is unclear. PHF8 binds to trimethylated histone H3 lysine 4 (H3K4me3), influencing its demethylase specificity: in the absence of H3K4me3, it has weak activity towards H3K9Me2, but when bound to H3K4me3, its activity towards H3K9Me2 is significantly enhanced. PHF8 positively regulates the transcription of the histone demethylase KDM5C, working synergistically with the transcription factor ARX. This synergy may be linked to the enrichment of H3K4me3 in regulatory elements. PHF8 interacts with various proteins involved in transcription and chromatin modification, including POLR1B, UBTF, SETD1A, HCFC1, E2F1, ZNF711, and ZNF263. At the SIX3 promoter, it interacts with ZNF263 and other chromatin modifiers to repress transcription.
PHF8 is also known as JHDM1F, KDM7B, MRXSSD, ZNF422.
