Venn diagram of PARP1-ChIP, TET1-ChIP and MeDIP in bone marrow-derived human mesenchymal stem cell
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE178805 | GEO | 2021/06/25
REPOSITORIES: GEO
Similar Datasets
Project description:Venn diagram of PARP1-ChIP, TET1-ChIP and MeDIP in bone marrow-derived human mesenchymal stem cell
| PRJNA741114 | ENA
Project description:BACKGROUND & AIMS: The immune system comprises an innate and an adaptive immune response to combat pathogenic agents. The human enteropathogen Salmonella enterica serovar Typhimurium invades the intestinal mucosa and triggers an early innate pro-inflammatory host gene response, which results in diarrheal disease. Several host factors are involved in the acute early response to Salmonella infection. Transcription factors and transcription co-regulators have an especially important function, because they are required for the expression and synthesis of pro-inflammatory cytokines, chemokines and adhesion molecules. A central transcription factor involved in inflammation is NF-κB, which requires the nuclear protein PARP1 as co-factor for the expression of some of its target genes. Here, we investigated the role of PARP1 during Salmonella infection using a mouse model for Salmonella-induced colitis. METHODS: To study enterocolitis by Salmonella Typhimurium, an established mouse model system, which relies on streptomycin-pretreatment prior to Salmonella infection, was employed. Histopathologic signs of inflammation and cecum colonization at various time-points after infection of wild type and PARP1 knockout mice were analyzed. PARP1 expression in the gut mucosa was studied by quantitative RT-PCR, Western blot and immunofluorescence. Gene expression profiles of infected and control infected mice in the wild type or PARP1 knockout background were obtained by whole mouse genome arrays and confirmed by quantitative RT-PCR. 2 genotypes (wildtype, PARP1 knockout), 2 treatments (Salmonella SB300 infection, Salmonella SB161 control infection), 2 time-points (6h, 10h). 2-3 replicates/condition.
2010-05-27 | E-GEOD-19174 | biostudies-arrayexpress
Project description:Poly(ADP-ribose) polymerase 1 (PARP1) is a highly conserved nuclear protein in multicellular organisms that modulates chromatin opening, and by doing so, it plays a significant role in gene expression regulation during development and differentiation. Despite its significance, all reported Parp1 total knockout mice strains are viable and fertile with no developmental anomalies. It was previously believed that functional redundancy with other PARP family members explain such a controversy. PARP2 is the main candidate to fulfill PARP1 functions in Parp1 knockout mice. Indeed, Parp1 Parp2 double knockout mice are arrested early in development and unable to proceed through gastrulation. However, while PARP2 has similar catalytic domain to PARP1, it lacks other domains that play important regulatory roles, thus making the lack of developmental problems in Parp1 mice total knockouts highly unlikely. To address this question, we checked the best investigated and publicly available Parp1 knockout mice strain. We found that Parp1 is still expressed in these mice, based on the presence of its mRNA transcript. Contrary to prior assumptions, we identified persistent mRNA expression in knockout mice, albeit at reduced levels. Detailed transcript analysis revealed an alternatively spliced PARP1 variant lacking exon two with introduced artificial cassette. Subsequent protein analysis confirmed the existence of a truncated PARP1 protein in knockout mice. We established embryonic stem cell lines from knockout mice and revealed the presence of pADPr. The decreased level of pADPr was detected in knockout ES cells with Western Blotting analysis, but immunofluorescence staining didn’t detect any difference in distribution or level of pADPr in nuclei of knockout ES cells compared to control ones. Moreover, in double Parp1 Parg mutant ES cells the accumulation of pADPr greatly exceeded its amount in normal and even in hypomorph Parg mutant ES cells, suggesting the presence of functionally active PARP1. Therefore, our findings challenge the conventional understanding of PARP1 depletion effects.
2024-07-15 | GSE248429 | GEO
Project description:BACKGROUND & AIMS: The immune system comprises an innate and an adaptive immune response to combat pathogenic agents. The human enteropathogen Salmonella enterica serovar Typhimurium invades the intestinal mucosa and triggers an early innate pro-inflammatory host gene response, which results in diarrheal disease. Several host factors are involved in the acute early response to Salmonella infection. Transcription factors and transcription co-regulators have an especially important function, because they are required for the expression and synthesis of pro-inflammatory cytokines, chemokines and adhesion molecules. A central transcription factor involved in inflammation is NF-κB, which requires the nuclear protein PARP1 as co-factor for the expression of some of its target genes. Here, we investigated the role of PARP1 during Salmonella infection using a mouse model for Salmonella-induced colitis. METHODS: To study enterocolitis by Salmonella Typhimurium, an established mouse model system, which relies on streptomycin-pretreatment prior to Salmonella infection, was employed. Histopathologic signs of inflammation and cecum colonization at various time-points after infection of wild type and PARP1 knockout mice were analyzed. PARP1 expression in the gut mucosa was studied by quantitative RT-PCR, Western blot and immunofluorescence. Gene expression profiles of infected and control infected mice in the wild type or PARP1 knockout background were obtained by whole mouse genome arrays and confirmed by quantitative RT-PCR.
2010-05-01 | GSE19174 | GEO
Project description:We have completed the high quality reference genome for domestic sheep (Oar v3.1). Early-stage Illumina GA sequence platform sequenced less reads in high GC content regions than in other regions. To read through higher GC content regions, we generated 2 Gb MeDIP-seq data for filling gaps in sheep reference genome assembly.
2014-06-06 | E-GEOD-56644 | biostudies-arrayexpress
Project description:Trabectedin is a DNA-damaging agent with a peculiar mechanism of action; it traps the DNA repair machinery leading to DNA single- and double-strand breaks, particularly in BRCA1/2-deficient tumors. We hypothesized that trabectedin-induced DNA damage might activate PARP1 (a DNA-repair machinery key player), and consequently, PARP1 inhibition would perpetuate trabectedin-induced DNA damage. In several tumor histotypes, we demonstrated a different degree of synergism between trabectedin and PARP1 inhibitors (PARP1-Is). Independent of BRCA1/2 status, PARP1 expression dictated the degree of synergism. Namely, silenced PARP1 reduced trabectedin-PARP1-Is synergism, whereas overexpressed PARP1 increased combination efficacy. High-PARP1 expression and specific gene signatures associated with DNA damage response and repair (DDR-R) were predictive of trabectedin+PARP1-I synergy. These findings pave the way for the clinical development of this novel combination therapy, as well as evaluation of PARP1 expression and DDR-R signatures in tumor samples as predictive biomarkers of response
2017-06-12 | GSE77175 | GEO
Project description:Recent studies have implicated PARP1 in alternative splicing regulation. In addition, PARP1 has been shown to bind RNA in vivo suggesting that it is an RNA-binding protein (RBP). However, a detailed knowledge of the RNA-targets as well as the RNA binding region of PARP1 is unknown. We used Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) in HeLa cells and identified a largely overlapping set ∼22142 of PARP1-RNA binding peaks mapping to mRNAs, of which ∼20484 sites are located in the intronic regions of genes. PARP1 preferentially bound RNA containing a Guanine-rich sequences. Using a bayesian model, we determined positional effects of PARP1 on exon skipping: PARP1 binding upstream and downstream to the skipped exons generally promoted exon inclusion, whereas binding on exons and closer to the skipped exon, promoted exon skipping. Finally, using truncation mutants, we narrowed the PARP1-RNA binding domain to the amino terminus region of the protein. Such studies on transcriptome-wide mapping of RNA-targets by PARP1, present the first step into understanding the role of PARP1 and RNA biogenesis. Our understanding of the role of PARPs and PAR in the transcriptional and post-transcriptional regulation of gene expression through modulation of RNA is still in the early stages. Continued identification and characterization of the functional interplay between PARPs and RNA may provide important insights into the role of PARPs in RNA regulation.
2018-02-14 | GSE95360 | GEO
Project description:Trabectedin is a DNA-damaging agent with a peculiar mechanism of action; it traps the DNA repair machinery leading to DNA single- and double-strand breaks, particularly in BRCA1/2-deficient tumors. We hypothesized that trabectedin-induced DNA damage might activate PARP1 (a DNA-repair machinery key player), and consequently, PARP1 inhibition would perpetuate trabectedin-induced DNA damage. In several tumor histotypes, we demonstrated a different degree of synergism between trabectedin and PARP1 inhibitors (PARP1-Is). Independent of BRCA1/2 status, PARP1 expression dictated the degree of synergism. Namely, silenced PARP1 reduced trabectedin-PARP1-Is synergism, whereas overexpressed PARP1 increased combination efficacy. High-PARP1 expression and specific gene signatures associated with DNA damage response and repair (DDR-R) were predictive of trabectedin+PARP1-I synergy. These findings pave the way for the clinical development of this novel combination therapy, as well as evaluation of PARP1 expression and DDR-R signatures in tumor samples as predictive biomarkers of response.
2017-06-12 | GSE76981 | GEO
Project description:Focused PARP1 mutagenesis screen for talazoparib resistance in HeLa-PARP1-GFP and SUM149-GFP cells
| PRJEB24332 | ENA