Genomewide analysis of the human p53 transcriptional network unveils a lncRNA tumor suppressor signature (ChIP-seq)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE58506 | GEO | 2014/12/22
SECONDARY ACCESSION(S): PRJNA252830
REPOSITORIES: GEO
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Project description:We report the application of high-throughput sequencing to performed the p53 regulated trancriptome in HCT116 colon cancer cells treated with the DNA damage 5FU. To study the direct targets of p53 we performed ChIP-seq to deterrmined the p53 biding sites and associated with the expression levels. With this study we identified the new genomic regions regulated by p53 and with special attention in those regions that are significally expressed by DNA damage and and are non- coding. HCT116 p53 wt cell transfected with the ASO-SC, ASO lncRNA-1 and ASO unassigned-1 for depletion of this new lncRNAs and treated with the DNA damage drug 5FU for 12h were analyzed in the affimetrix platform HTA2.
2014-12-22 | E-GEOD-58409 | biostudies-arrayexpress
Project description:We report the application of high-throughput sequencing to performed the p53 regulated trancriptome in HCT116 colon cancer cells treated with the DNA damage 5FU. To study the direct targets of p53 we performed ChIP-seq to deterrmined the p53 biding sites and associated with the expression levels. With this study we identified the new genomic regions regulated by p53 and with special attention in those regions that are significally expressed by DNA damage and and are non- coding.
2014-12-22 | GSE58409 | GEO
Project description:We report the application of high-throughput sequencing to performed the p53 regulated trancriptome in HCT116 colon cancer cells treated with the DNA damage 5FU. To study the direct targets of p53 we performed ChIP-seq to deterrmined the p53 biding sites and associated with the expression levels. With this study we identified the new genomic regions regulated by p53 and with special attention in those regions that are non coding and are differentially expressed by the DNA damage drug.
2014-12-22 | GSE58507 | GEO
Project description:We report the application of high-throughput sequencing to performed the p53 regulated trancriptome in HCT116 colon cancer cells treated with the DNA damage 5FU. To study the direct targets of p53 we performed ChIP-seq to deterrmined the p53 biding sites and associated with the expression levels. With this study we identified the new genomic regions regulated by p53 and with special attention in those regions that are non coding and are differentially expressed by the DNA damage drug. Description of the p53 transcriptome in HCT116 colon cancer cell line. The RNA-seq libraries were prepared from purified poly-A+ RNA from untreated and 5-Fluorouracil treated p53 +/+ HCT116 cells for 4 and 12h, including two independent samples for the time 12h. Paired-end and strand specific RNA sequencing libraries were prepared according to Illumina instructions and sequenced on HiSeq 2000 (Ilumina) with sequence length of 150 bp. Raw sequencing data were alignment to the human genome (hg19) using Tophat mapper.
2014-12-22 | E-GEOD-58507 | biostudies-arrayexpress
Project description:Natural chemical modifications to 5-formyluracil (5fU) has been identified as an important oxidative nucleobase modification, is present in the genomes of many cell types. However, its distribution in genome is poorly understood. Herein, we present a selec-tive labeling and pull-down strategy termed fU-Seq for genome-wide 5fU profiling in mouse hippocampus and human thyroid carcinoma tissues. The mainly essence is using an azido modified (2-benzimidazolyl)acetonitrile derivative that selectively labels 5fU. Surprisingly, 5fU is highly enriched at intergenic and intron, and 5fU-rich regions are positively correlated with H3K27me3 and negatively correlated with H3K27ac, indicating that 5fU is associated with transcription. Collectively, the sequencing of 5fU allow comprehensive analysis of 5fU in genome and provide effective technology for mapping and paves the way for addressing biological and chemical questions regarding this nucleobase modification and for revealing its potential roles in epigenetics.
2018-11-28 | GSE115918 | GEO
Project description:The tumor suppressor p53 regulates the differentiation of embryonic stem (ES) cells upon DNA damage. However, our understanding of this critical tumor suppressive role of p53 in ES cells is limited, mainly because of the lack of molecular mechanism. Here, we report a widespread cross-regulation of p53-mediated DNA damage signaling and the pluripotent gene network in ES cells using chromatin-immunoprecipitation assay-based sequencing (ChIP-seq) and gene expression microarray. Upon DNA damage, p53 directly regulates the transcription of 3644 genes (p<0.005) in mouse ES cells. Genome-wide analysis revealed a dramatic difference between the regulation of p53-activated and -repressed genes. p53 mainly regulates the promoter regions of activated genes, whereas the main regulatory regions for repressed genes reside in distal regions. Among p53-repressed genes, many are pluripotent transcription factors of ES cells, such as Oct4, Nanog, Sox2, Esrrb, c-Myc, n-Myc and Sall4. Strikingly, these transcriptional factors also directly regulate the transcription of the Trp53 gene, highlighting a previously under-estimated transcriptional regulation of p53 in ES cells. Therefore, p53 signaling and ES pluripotent transcriptional networks form an intertwined circuitry. Together, our results provide mechanistic insights into the crosstalk of p53-mediated DNA damage and ES cell "stemness" transcriptional gene networks and shed light on the tumor suppressive function of p53 in ES cells. The goal of this experiment is to identify the gene expression changes after adriamycin treatment in a p53-dependent manner. Total six samples: triplicates for untreated mES cells and triplicates for mES cells treated with adriamycin.
2012-03-05 | E-GEOD-26360 | biostudies-arrayexpress
Project description:The tumor suppressor p53 regulates the differentiation of embryonic stem (ES) cells upon DNA damage. However, our understanding of this critical tumor suppressive role of p53 in ES cells is limited, mainly because of the lack of molecular mechanism. Here, we report a widespread cross-regulation of p53-mediated DNA damage signaling and the pluripotent gene network in ES cells using chromatin-immunoprecipitation assay-based sequencing (ChIP-seq) and gene expression microarray. Upon DNA damage, p53 directly regulates the transcription of 3644 genes (p<0.005) in mouse ES cells. Genome-wide analysis revealed a dramatic difference between the regulation of p53-activated and -repressed genes. p53 mainly regulates the promoter regions of activated genes, whereas the main regulatory regions for repressed genes reside in distal regions. Among p53-repressed genes, many are pluripotent transcription factors of ES cells, such as Oct4, Nanog, Sox2, Esrrb, c-Myc, n-Myc and Sall4. Strikingly, these transcriptional factors also directly regulate the transcription of the Trp53 gene, highlighting a previously under-estimated transcriptional regulation of p53 in ES cells. Therefore, p53 signaling and ES pluripotent transcriptional networks form an intertwined circuitry. Together, our results provide mechanistic insights into the crosstalk of p53-mediated DNA damage and ES cell "stemness" transcriptional gene networks and shed light on the tumor suppressive function of p53 in ES cells.
2012-03-05 | GSE26360 | GEO
Project description:A subset of our SLNs would be upregulated by Nutlin-3 and down-regulated by 5-FU and that this differential regulation could potentially explain how cell fate choice is determined SLNs as a group were largely members of pathways parallel to p53, in the sense that very few of them displayed significant changes in mRNA expression after Nutlin-3 or 5FU treatment RNA was harvested from cells treated with Nutlin-3, 5FU, or DMSO, for 12 hours using the RNeasy kit (Qiagen). cDNAs were synthesized and labeled with the Genechip Whole Transcript Sense Target Labeling Kit (Affymetrix) per the manufacturer’s instructions and hybridized to Human Exon 1.0 ST arrays (AffyMetrix)
2012-03-20 | E-GEOD-36593 | biostudies-arrayexpress
Project description:We explored the combinatorial interactions between p53, estrogen receptors and NFkB using the breast adenocarcinoma-derived MCF7 cells. Recently, we have established that p53 can modulate transcription also through non-canonical response elements (REs), consisting of half-sites and ¾ sites. In particular, we identified a half-site p53 response element in the promoter of FLT1/VEGFR-I gene that was required but not sufficient for the p53 responsiveness of the promoter. The transcriptional control required also estrogen receptor (ER) half-sites (EREs) located in close proximity to the p53 RE. Further studies led us to establish that p53-mediated transcription from the FLT1 half site RE is dependent on ER binding at the EREs and strongly influenced by the level of ER proteins, and the specific nature of the p53-inducing stress as well as ER ligand. In another study we found an enrichment of NFkB REs nearby p53 REs in p53 target genes, suggesting an additional mode of functional interactions between these two transcription factors. To identify at a genome scale the transcriptional network that selectively responds to the concomitant activation of p53, ER and/or NFkB, we measured gene expression upon treatment with specific chemotherapeutic agents combined with 17-β estradiol (E2) and/or the inflammatory cytokine TNFα. Firstly we measured using MCF7 cells growing in estrogen-depleted media the transcriptome changes induced by doxorubicin (doxo) and 5-fluorouracil (5FU), two different drugs both able to stabilize and activate the p53 protein. We next obtained the expression profiles in the presence of E2 with or without doxo or 5FU. We also measured transcriptome changes in response to TNFαalone or in combination with doxo and/or E2. All these analyses were conducted using the same batch of MCF7 cells (wild type for p53, ERα, ERβ -weakly-, and NFkB positive) that we had previously used to characterize the cis-mediated transcriptional cooperation between p53 and ER at the FLT1 gene. Keywords: transcription factor, transcriptional networks, p53, ER, NFkB, p53-ER-NFkB crosstalk, doxorubicin, 5-fluorouracil, 17-β estradiol, TNFα, combined genotoxic, estrogenic and inflammatory responses, composite DNA binding site signatures, MCF7. The cooperation at the transcriptional level among p53, ERs and NFkB was analyzed by transcriptome analysis in response to different stimuli (doxo or 5FU, E2, TNFα). To identify mRNA molecules that would be modulated by the coordinated activity of the three TFs, gene expression signals derived from the combinatorial treatment were compared by microarrays analyses to those obtained from each drug when individually administered. Total RNA was isolated from MCF7 cells grown in estrogen-depleted medium and treated so as to stimulate the activity of the three different transcription factors (p53, ERs and NFkB). Cells lysates were collected after 10 hours from the treatments. All experiments were run from triplicate to septuples.
2011-06-01 | E-GEOD-24065 | biostudies-arrayexpress