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PHF8 mediates histone demethylation events in cell cycle progression [expression]

ABSTRACT: While reversible histone modifications are linked to an ever-expanding range of biological functions, the demethylases for histone H4 lysine 20 and their potential regulatory roles remain unknown. Here, we report that the PHD and Jumonji C (JmjC) domain-containing protein, PHF8, while utilizing multiple substrates, including H3K9me1/2 and H3K27me2, also functions as an H4K20me1 demethylase. PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1/S transition in conjunction with E2F1, HCF-1 and Set1A, at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is apparently required for the accumulation of H4K20me1 during early mitosis, which might represent a component of the Condensin II loading process. Accordingly, the HEAT repeat clusters in two non-SMC Condensin II subunits, N-CAPD3 and N-CAPG2, are capable of recognizing H4K20me1, and ChIP-seq. analysis demonstrate a significant overlap of Condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, the identification and characterization of an H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression. Keywords: Expression profiling by array HeLa cells were transfected with either control or PHF8 siRNAs. Experiments were performed in biological duplicates. RNA were extracted and sujected to microarray analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: BOGDAN TANASA

PROVIDER: E-GEOD-22477 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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PHF8 mediates histone demethylation events in cell cycle progression [ChIP-Seq]

Project description:While reversible histone modifications are linked to an ever-expanding range of biological functions, the demethylases for histone H4 lysine 20 and their potential regulatory roles remain unknown. Here, we report that the PHD and Jumonji C (JmjC) domain-containing protein, PHF8, while utilizing multiple substrates, including H3K9me1/2 and H3K27me2, also functions as an H4K20me1 demethylase. PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1/S transition in conjunction with E2F1, HCF-1 and Set1A, at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is apparently required for the accumulation of H4K20me1 during early mitosis, which might represent a component of the Condensin II loading process. Accordingly, the HEAT repeat clusters in two non-SMC Condensin II subunits, N-CAPD3 and N-CAPG2, are capable of recognizing H4K20me1, and ChIP-seq. analysis demonstrate a significant overlap of Condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, the identification and characterization of an H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression. unsynchronized HeLa cells were used to profile H3K4me2 and E2F1; unsynchronized or G1 or G1/S synchronized HeLa cells were used to profile PHF8; M phase synchronized HeLa cells were used to profile SMC4 and H4K20me1

2010-09-01 | E-GEOD-22478 | biostudies-arrayexpress

PHF8 mediates histone demethylation events in cell cycle progression [ChIP-Seq]

2010-09-01 | GSE22478 | GEO

PHF8 mediates histone demethylation events in cell cycle progression [expression]

2010-09-01 | GSE22477 | GEO

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

Project description: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.

2010-07-14 | E-GEOD-21555 | biostudies-arrayexpress

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

Project description: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. 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.

2010-07-14 | E-GEOD-21108 | biostudies-arrayexpress

PHF8 targets histone methylation and RNA polymerase II to activate transcription

Project description:Mutations in PHF8 are associated with X-linked mental retardationand cleft lip/cleft palate. PHF8 contains a plant homeodomain(PHD) in its N-terminus and is member of a family of JmjC-domaincontaining proteins. While PHDs can act as methyl lysine recognitionmotifs, JmjC-domains can catalyze lysine demethylation. Here,we show that PHF8 is a histone demethylase that removes repressivehistone H3 dimethyl lysine 9 marks. Our biochemical analysisrevealed specific association of the PHF8 PHD domain with histoneH3 trimethylated at lysine 4 (H3K4me3). Chromatin-immunoprecipitationfollowed by high throughput sequencing indicated that PHF8 isenriched at transcription start sites of many active or poisedgenes, mirroring the presence of RNA polymerase II (RNAPII)and of H3K4me3-bearing nucleosomes. We show that PHF8 can actas a transcriptional co-activator and its activation functionlargely depends on binding of the PHD to H3K4me3. Furthermore,we present evidence for direct interaction of PHF8 with theC-terminal domain of RNAPII. Importantly, a PHF8 disease mutantis defective in demethylation and in co-activation. This isthe first demonstration of a chromatin-modifying enzyme whichis globally recruited to promoters through its association withH3K4me3 and RNAPII. This SuperSeries is composed of the following subset Series: GSE20563: Knockdown of PHF8 in HeLa S3 cells GSE20725: ChIP-Seq of PHF8 and H3K4me3 Refer to individual Series

2010-04-26 | E-GEOD-20753 | biostudies-arrayexpress

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

2010-07-14 | GSE21108 | GEO

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

2010-07-14 | GSE21555 | GEO

Knockdown of PHF8 in HeLa S3 cells

Project description:PHF8 is an H3K9me2 demethylase, interacts with H3K4me3 and RNA Polymerase II, is enriched at thousands of transcription start sites and can act as a transcriptional co-activator. In the following experiment we wanted to analyze the impact of PHF8-knockdown on transcript levels in HeLa cells.

2010-04-27 | GSE20563 | GEO

ChIP-seq of PHF8 and H3K4me3

Project description:PHF8 is an H3K9me2 demethylase, interacts with H3K4me3 and RNA Polymerase II, is enriched at thousands of transcription start sites and can act as a transcriptional co-activator. ChIP-seq of PHF8 in HeLa, 293T and Hs68 cells, and of H3K4me3 in Hs68 fibroblasts was performed. Normal IgG-IP or input DNA served as negative controls.

2010-04-27 | E-GEOD-20725 | biostudies-arrayexpress

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