The mental retardation gene PHF8 mediates histone H4K20/H3K9 demethylation and regulates zebrafish brain apoptosis and craniofacial development: expression analysis

ABSTRACT: PHF8 (PHD Finger 8) mutations have been found in patients with X-linked mental retardation (XLMR) and craniofacial deformities. Here we identify PHF8 as the first enzyme that mediates demethylation of mono-methylated histone H4 lysine (K) 20 (H4K20me1), with additional activities towards H3K9me2/1 and H3K27me2. Patient mutations significantly compromise the demethylase activity, indicating functional importance. ChIP-seq identified PHF8 near the transcription start sites (TSS) of over 7000 target genes as well as in gene bodies and intergenic regions. PHF8 depletion resulted in up-regulation of H4K20me1 and H3K9me1 at the TSS-associated sites, and H3K9me2 in the gene bodies and intergenic regions, respectively, demonstrating differential substrate specificities at different target genomic locations. PHF8 depletion at the TSS results in decreased target gene expression, which is coincident with increased occupancy of the protein L3MBTL1 previously shown to induce chromatin compaction via binding to lower methyl states including H4K20me1 and H3K9me1. PHF8 RNAi and control RNAi stable HeLa cell lines were established. RNA were isolated from triplicate cell cultures. RNAs were subject to microarray expression analysis. Hybridizations were performed in duplicate.

ORGANISM(S): Homo sapiens

SUBMITTER: Hank qi 

PROVIDER: E-GEOD-21555 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress