PARP1 binds and regulates expression of extracellular matrix genes in renal tubular epithelial cells [RIP-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE157558 | GEO | 2022/05/06
REPOSITORIES: GEO
Similar Datasets
Project description:PARP1 (Poly adenosine diphosphate ribose polymerase 1) is a ribozyme activated by a broken single-stranded DNA. Recent studies implicate PARP1 not only binds DNA but also be an RNA-binding protein. PARP1 participate in the regulation of renal ischemia-reperfusion injury through binding RNAs, but the mechanism is not clear. Reduced levels of PARP1 led to a significant decrease in cell proliferation and necrosis in the renal ischemia-reperfusion injury cells. In this study, RNA‑seq analysis of the transcriptomes of HK-2 cells with PARP1 knockdown, revealed that genes related extracellular matrix organization and immune response were under global transcriptional regulation.
2022-05-06 | GSE157557 | 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:GATA4 regulates the liver development, but it's function and the gene transcriptional programs it regulates in the adult liver is unknown. In this study, we determined the genome-wide occupancy sites of GATA4 by performing ChIP-seq of whole livers. We have identified 4409 GATA4 enrichment peaks using two peak calling methods and irreproducible discovery rate (IDR) analysis. This corresponds to 3075 genes with GATA4 peaks within -5 kb of transcription start site (TSS) and +5 kb of transcription termination site (TTS). MEME analysis shows that approximately 90% of the peaks have the WGATAR motif, suggesting direct binding by GATA4. The peaks containing the WGATAR motif have a ChIP-seq higher tag enrichment score than peaks lacking the motif. Genome Regions Enrichment of Annotations Tool (GREAT) analysis of genes bound by GATA4 identified ontologies with liver specific functions. In summary, our study shows for the first time genome-wide occupancy profile of GATA4in the adult mouse liver. ChIP-sequencing of whole mouse livers from 2-3 month old mice
2013-11-07 | E-GEOD-49131 | 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: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: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:Poly-(ADP-ribose) polymerase inhibitors (PARPi) elicit anti-tumour activity in homologous recombination defective cancers by promoting cytotoxic, chromatin-bound, “trapped” PARP1 DNA lesions. How cells process trapped PARP1 remains unclear. By exploiting wild-type or trapping-resistant PARP1 transgenes combined with rapid immunoprecipitation mass-spectrometry of endogenous proteins (RIME) and Apex2-proximity labelling, we generated proteomic profiles of trapped and non-trapped PARP1 complexes. This combined approach identified an interaction between PARP1 and the ubiquitin system including its central component - the ubiquitin-regulated p97 ATPase (aka VCP).
2021-10-05 | PXD024337 | Pride
Project description:GATA4 regulates the liver development, but it's function and the gene transcriptional programs it regulates in the adult liver is unknown. In this study, we determined the genome-wide occupancy sites of GATA4 by performing ChIP-seq of whole livers. We have identified 4409 GATA4 enrichment peaks using two peak calling methods and irreproducible discovery rate (IDR) analysis. This corresponds to 3075 genes with GATA4 peaks within -5 kb of transcription start site (TSS) and +5 kb of transcription termination site (TTS). MEME analysis shows that approximately 90% of the peaks have the WGATAR motif, suggesting direct binding by GATA4. The peaks containing the WGATAR motif have a ChIP-seq higher tag enrichment score than peaks lacking the motif. Genome Regions Enrichment of Annotations Tool (GREAT) analysis of genes bound by GATA4 identified ontologies with liver specific functions. In summary, our study shows for the first time genome-wide occupancy profile of GATA4in the adult mouse liver.
2013-11-07 | GSE49131 | GEO
Project description:The project is about studying the dynamics of PARP1 when bound to DNA and HPF1.
2022-02-17 | PXD026580 | Pride
Project description:Focused PARP1 mutagenesis screen for talazoparib resistance in HeLa-PARP1-GFP and SUM149-GFP cells
| PRJEB24332 | ENA