Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-20193
PROVIDER: PRJNA125693 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Full title: Altered levels of MOF (member of MYST family histone acetyl transferase) and decreased levels of H4K16ac correlate with a defective DNA damage response (DDR). The human MOF gene encodes a protein that specifically acetylates histone H4 at lysine 16 (H4K16ac). Here we show that altered levels of H4K16ac correlate with a defective DNA damage response (DDR) to ionizing radiation (IR). The defect however is not due to altered expression of proteins involved in DDR. Specific inhibition of H4K16ac deacetylation in MOF-depleted cells rescued IR-induced abrogation of DDR. MOF was found associated with DNA-dependent protein kinase catalytic subunit (DNAPKcs), a protein involved in non-homologous end joining (NHEJ) repair, whose ATMdependent IR-induced phosphorylation was abrogated in MOF-depleted cells. Our data indicate that MOF depletion greatly decreased the repair of DNA double-strand breaks (DSBs) by NHEJ and homologous recombination (HR). In addition, the MOF protein activity associates with chromatin upon DNA damage and colocalizes with the synaptonemal complex in male meiocytes. We propose that MOF, through H4K16ac, plays a critical role in the cellular DNA damage response. Keywords: Cell type comparison
2010-03-15 | GSE20193 | GEO
Project description:Full title: Altered levels of MOF (member of MYST family histone acetyl transferase) and decreased levels of H4K16ac correlate with a defective DNA damage response (DDR). The human MOF gene encodes a protein that specifically acetylates histone H4 at lysine 16 (H4K16ac). Here we show that altered levels of H4K16ac correlate with a defective DNA damage response (DDR) to ionizing radiation (IR). The defect however is not due to altered expression of proteins involved in DDR. Specific inhibition of H4K16ac deacetylation in MOF-depleted cells rescued IR-induced abrogation of DDR. MOF was found associated with DNA-dependent protein kinase catalytic subunit (DNAPKcs), a protein involved in non-homologous end joining (NHEJ) repair, whose ATMdependent IR-induced phosphorylation was abrogated in MOF-depleted cells. Our data indicate that MOF depletion greatly decreased the repair of DNA double-strand breaks (DSBs) by NHEJ and homologous recombination (HR). In addition, the MOF protein activity associates with chromatin upon DNA damage and colocalizes with the synaptonemal complex in male meiocytes. We propose that MOF, through H4K16ac, plays a critical role in the cellular DNA damage response. Keywords: Cell type comparison HEK293 cells were transfected with plasmids encoding hMOF for over-expression of the histone acetyl transferase that leads to elevated levels of acetylation of Lysine 16 of histone H4. siRNA mediated knock-down of hMOF was performed to deplete the H4K16ac levels. Total RNA samples for expression profiling was obtained from wild type (293 cells without any treatment), hMOF over-expressed and hMOF knock-down 293 cell lines. Each sample was analyzed in triplicates using EGPF dsRNA treated samples as control.
2010-03-23 | E-GEOD-20193 | biostudies-arrayexpress
Project description:Altered levels of MOF and decreased levels of H4K16ac correlate with a defective DNA damage response (DDR).
2015-09-15 | E-GEOD-20193 | ExpressionAtlas
Project description:Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors. 4 cell lines, all in duplicates
2016-03-29 | E-GEOD-78717 | biostudies-arrayexpress
Project description:Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors. We isolated RNA from Ataxia-telangiectasia (A-T) patient fibroblast derived iPS cells and A-T patient fibroblasts for hybridization to the Affymetrix gene expression microarrays.
2016-03-29 | E-GEOD-78716 | biostudies-arrayexpress
Project description:ChIP-Seq profiles of MSL1, MSL2, MSl3, MOF, MLE, H4K16ac and RNA Polymerase II phosphorlyated on Serine 5 in Drosophila S2 cells MSL1, MSL2, MSL3, MOF, MLE, H4K16ac and RNA Polymerase II phosphorlyated on Serine 5 ChIP in Drosophila S2 cells. 1-3 biological replicates per experiment. Performed in single-read and paired-end read mode.
2012-12-11 | E-GEOD-37864 | biostudies-arrayexpress
Project description:Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors. We isolated genomic DNA from Ataxia-telangiectasia (A-T) iPSC cells derived from patient fibroblasts virus and episomal vectors, coresponding fibroblasts, normal human fibroblast derived iPSCcells, for hybridization to the Affymetrix Genome-Wide Human SNP 6.0 Array.
2016-03-29 | E-GEOD-78715 | biostudies-arrayexpress
Project description:Partial hepatectomy (PH) imposes increased protein synthesis demands on remaining hepatocytes. Activation of IRE1α, a key sensor of endoplasmic reticulum (ER) stress, elicits XBP1 mRNA splicing and production of XBP1 protein, a main trigger of the unfolded protein response (UPR). Using genome-wide ChIPseq analysis we have explored the role of XBP1 during liver regeneration. XBP1 was induced in liver at 6h after PH in an IL-6 dependent manner. After PH, XBP1 silencing caused persistent ER stress, defective acute phase response (APR), increased hepatocellular damage and regenerative delay. At 6h post-PH, XBP1 bound an increased number of genes implicated in proteostasis, APR, metabolism, antioxidant defense and DNA damage response (DDR). ). XBP1 was linked to regulatory sequences containing canonical UPR motifs as well as motifs characteristic of other nuclear factors suggesting molecular interactions during liver regeneration. Upon PH, XBP1 bound the promoter of STAT3, a molecule downregulated in XBP1-silenced livers. XBP1 was indispensable for ser727-STAT3 phosphorylation, a post-translational modification implicated in cell proliferation and DNA damage repair. During active DNA replication XBP1 deficient livers showed high levels of the DNA double-strand break marker γ-H2AX, in association with defective upregulation of Eme1 and Fen1, two main executors of DDR. In conclusion, XBP1 is induced after PH and co-regulates UPR, APR and DDR during liver regeneration.
2017-01-17 | GSE86048 | GEO
Project description:Histone methyltransferase MLL4 is centrally involved in transcriptional regulation and is often mutated in human diseases, including cancer and developmental disorders. MLL4 contains a catalytic SET domain that mono-methylates histone H3K4 and seven PHD fingers of unclear function. Here, we identify the PHD6 finger of MLL4 (MLL4-PHD6) as the first selective reader of the epigenetic modification H4K16ac. The solution NMR structure of MLL4-PHD6 in complex with a H4K16ac peptide along with binding and mutational analyses reveal unique mechanistic features underlying recognition of H4K16ac. Genomic studies show that one third of MLL4 chromatin binding sites overlap with H4K16ac-enriched regions in vivo and that MLL4 occupancy in a set of genomic targets depends on the acetyltransferase activity of MOF, a H4K16ac-specific acetyltransferase. The recognition of H4K16ac is conserved in the PHD7 finger of paralogous MLL3. Together, our findings highlight a novel acetyllysine reader and suggest that selective targeting of H4K16ac by MLL4 provides a direct functional link between MLL4, MOF and H4K16 acetylation.
2019-04-20 | GSE130091 | GEO
Project description:RNA splicing and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice we show that XAB2, the human homologue of the yeast pre-mRNA-splicing factor SYF1 has a functional role in Nucleotide Excision Repair (NER) and the DNA damage response (DDR) in mammals. XAB2 interacts with spliceosome factors and is part of the core spliceosome that binds to spliceosomal U4 and U6 snRNAs during hepatic development. Ablation of XAB2 leads to defective NER, intron retention, the aberrant accumulation of pre-mRNAs and to a faulty ATM/ATR DDR signaling. Using functional approaches, we find that XAB2 dissociates from RNA targets upon persistent DNA damage or transcription blockage and from spliceosomal RNAs in the NER-defective developing livers. Thus, XAB2 functionally links NER to the spliceosomal response to DNA damage during hepatic development with important ramifications for transcription-coupled DNA repair disorders.
2021-09-08 | PXD014084 | Pride