Abstract
Chromatin regulators play an important role in the development of human diseases. In this study, we focused on Plant Homeo Domain Finger protein 8 (PHF8), a chromatin regulator that has attracted special concern recently. PHF8 is a histone lysine demethylase ubiquitously expressed in nuclei. Mutations of PHF8 are associated with X-linked mental retardation. It usually functions as a transcriptional co-activator by associating with H3K4me3 and RNA polymerase II. We found that PHF8 may associate with another regulator, REST/NRSF, predominately at promoter regions via studying several published PHF8 chromatin immunoprecipitation-sequencing (ChIP-Seq) datasets. Our analysis suggested that PHF8 not only activates but may also repress gene expression.
Highlights
Chromatin regulators play an important role in the development of human diseases
As previous studies have already proved that PHF8 and E2F1 are co-factors, our results suggest that PHF8, E2F1 and REST are co-binding factors
PHF8 binds to a subset of E2F1 regulated genes, and functions in the regulation of cell cycle[5]. This analysis revealed that REST and E2F1 associate with PHF8 at a subset of PHF8 target gene promoters to influence gene expression
Summary
Chromatin regulators play an important role in the development of human diseases. In this study, we focused on Plant Homeo Domain Finger protein 8 (PHF8), a chromatin regulator that has attracted special concern recently. PHF8 is a JmjC domain-containing protein and erases repressive histone marks including H4K20me[1] and H3K9me1/24–7 It binds to H3K4me[3], an active histone mark usually located at transcription start sites (TSSs)[8,9], through its plant homeo-domain, and is recruited and enriched in gene promoters. Previous study demonstrated that KDM5C, a histone demethylase that targets H3K4me2/3, is recruited by the repressor protein REST/NRSF and is associated with XLMR14. These studies have revealed several important functions of PHF8, the regulatory functions of PHF8 remain poorly understood.
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