Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development

摘要: Mutations in the PHF8 gene, which encodes plant homeo domain (PHD) finger protein 8, are connected to X-linked mental retardation associated with cleft lip and palate. Two groups now report that is a histone demethylase activity against H4K20me1 (histone H4 lysine 20). Qi et al. role for regulating gene expression, as well neuronal cell survival craniofacial development zebrafish. The results suggest there may be link between methylation dynamics retardation. Liu show linked two distinct events during cell-cycle progression. recruited promoters of G1/S-phase genes where it removes contributes activation, whereas dissociation from chromatin prophase allows accumulate mitosis. JmjC domain-containing protein, has been (XLMR). These authors demonstrate H4K20me1. It expression XLMR. (XLMR) complex human disease causes intellectual disability1. Causal mutations have found approximately 90 genes2; however, molecular biological functions many these genetically defined XLMR remain unknown. (PHD (plant domain) 8) its patients deformities. Here we provide multiple lines evidence establishing first mono-methyl 20 (H4K20me1) demethylase, additional activities towards H3K9me1 me2. located around transcription start sites (TSS) ∼7,000 RefSeq bodies intergenic regions (non-TSS). depletion resulted upregulation at TSS H3K9me2 non-TSS sites, respectively, demonstrating differential substrate specificities different target locations. positively regulates dependent on H3K4me3-binding PHD catalytic domains. Importantly, patient significantly compromised function. zebrafish brain jaw development, thus providing potentially relevant context understanding clinical symptoms patients. Lastly, genetic supports model whereby part by directly homeodomain factor MSX1/MSXB, downstream signalling developmental pathways3. Our findings indicate an imbalance critical