ENAapplication/xmlftp.sra.ebi.ac.uk/vol1/fastq/SRR039/SRR039595/SRR039595.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR039/SRR039599/SRR039599.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR039/SRR039596/SRR039596.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR039/SRR039600/SRR039600.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR039/SRR039601/SRR039601.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR039/SRR039598/SRR039598.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR039/SRR039597/SRR039597.fastq.gzprimaryOK2000000GenomicsMultiomicsSystems Biology Center, NHLBI, NIHhttps://www.ebi.ac.uk/ena/browser/view/PRJNA126679Homo sapiensPHF8 (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. Overall design: HeLa cells stably expressing control and PHF8 shRNA were used to profile the histone modifications including H4K20me1, H3K9me1 and 2 by ChIP-seq. For PHF8 ChIP-seq, chromatin was obtained by formaldehyde cross-link and sonication. For chIP-seq of Histone modifcation, chromatin was prepared by MNase digestion to obtain mono-nucleosomes.ENAzebra fish, the brain, determination, caspase-dependent programmed cell death, Poor school performance, Intellectual disability, Caspase Dependent Apoptosis, Mental-retardation, type I programmed cell death, apoptotic programmed cell death, activation of apoptosis, Demethylations, zebra danio, Extrinsic Pathway Apoptoses, Oxidative, Programmed, synganglion, Type I, Cyprinus rerio, D. rerios, Oxidative Demethylation, Zebrafishes, Low intelligence, Dull intelligence, chemical analysis., Fishes, suprasegmental levels of nervous system, apoptosis activator activity, ZNF422, Intrinsic Pathway Apoptosis, Classic, B. rerio, Classic Apoptosis, execution phase of apoptotic process, Classical Apoptosis, Zebra Fishes, cranial skeleton development, programmed cell death by apoptosis, Brachydanio rerio frankei, Apoptosis, Danio rerio (Hamilton, cellular suicide, leopard danio, suprasegmental structures, Zebra Fish, cell suicide, Caspase-Dependent Apoptosis, PHF8, Oxidative Demethylations, apoptotic cell death, Demethylation, Cyprinus rerio Hamilton, nonspecific, encephalon, MRXSSD, signaling (initiator) caspase activity, induction of apoptosis, Intrinsic Pathway, Programmed Cell Death, Extrinsic Pathway Apoptosis, Danio rerio frankei, 1822), 1822, Brachydanio rerio, craniofacial development, Caspase-Dependent, Brachidanio rerio, apoptosis signaling, RGD1561065, 9830141C09Rik, Zebra, Danio rerio, apoptosis, Danio frankei, Mental retardation, Encephalon, demethylation, Nonprogressive intellectual disability, Nonprogressive mental retardation, INSDC_feature:gene, Cell Death, cranium development, danio, Zebra danios, Classic Apoptoses, Intrinsic Pathway Apoptoses, JHDM1F, Zebra danio, induction of apoptosis by p53, apoptotic program, osteocranium development, D. rerio, Extrinsic Pathway, commitment to apoptosis, mKIAA1111, assay, Mental deficiency, Classical, zebrafish, Apoptoseshuman being, human., man0.00.00.00.00.00falseHomo sapiensThe mental retardation gene PHF8 mediates histone H4K20/H3K9 demethylation and regulates zebrafish brain apoptosis and craniofacial development: ChIP-Seq analysis2022-05-122013-05-31PRJNA126679GSE21108206228539606