E-GEOD-20193
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA125693
PROVIDER: E-GEOD-20193 | ExpressionAtlas | 2015-09-15
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-20193-analysis-methods.tsv | Tabular | |||
| E-GEOD-20193-atlasExperimentSummary.Rdata | Rdata | |||
| E-GEOD-20193-configuration.xml | Xml | |||
| E-GEOD-20193-percentile-ranks.tsv | Tabular | |||
| E-GEOD-20193.condensed-sdrf.tsv | Tabular |
Items per page: 5 1 - 5 of 71 |
Similar Datasets
Project description:Altered levels of MOF and decreased levels of H4K16ac correlate with a defective DNA damage response (DDR).
| PRJNA125693 | ENA
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:Mouse models with defective DNA damage repair
| PRJNA492800 | ENA
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
Project description:Targetted metabolomics in U2OS PRDX1 WT and PRDX1-/- While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be achieved. Here, we investigate the metabolic enzymes and processes that are essential when cells are exposed to DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Subsequent analysis identified Peroxiredoxin 1, PRDX1, as fundamental for DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it is required to reduce DNA damage-induced nuclear reactive oxygen species levels. Moreover, PRDX1 controls aspartate availability, which is required for the DNA damage repair-induced upregulation of de novo nucleotide synthesis. Loss of PRDX1 leads to an impairment in the clearance of γΗ2ΑΧ nuclear foci, accumulation of replicative stress and cell proliferation defects, thus revealing a crucial role for PRDX1 as a DNA damage surveillance factor.
2022-07-19 | ST002234 | MetabolomicsWorkbench
Project description:Long-term perturbation of de novo chromatin assembly during DNA replication has profound effects on epigenome maintenance and cell fate. The early mechanistic origin of these defects is unknown. Here, we combine acute degradation of Chromatin Assembly Factor 1 (CAF-1), a key player in de novo chromatin assembly, with single-cell genomics, quantitative proteomics, and live-microscopy to uncover these initiating mechanisms in human cells. CAF-1 loss immediately slows down DNA replication speed and renders nascent DNA hyper-accessible. A rapid cellular response, distinct from canonical DNA damage signaling, is triggered and lowers histone mRNAs. As a result, histone variants usage and their modifications are altered, limiting transcriptional fidelity and delaying chromatin maturation within a single S-phase. This multi-level response induces a cell-cycle arrest after mitosis. Our work reveals the immediate consequences of defective de novo chromatin assembly during DNA replication, explaining how at later times the epigenome and cell fate can be altered.
2024-04-17 | GSE262518 | GEO
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