The effects of the global loss of DNA methylation on the functional cancer epigenome
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Fides Lay
PROVIDER: E-GEOD-58638 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Ablation of ERRalpha significantly delays ERBB2-induced mammary tumorigenesis and ERRalpha regulates genes of the ERBB2 amplicon. To further investigate the relationship between ERRalpha activity and RTK signaling, we mapped ERRalpha binding sites in SKBr3 cells upon EGF treatment or heregulin treatment. Inhibition of ERBB2 signaling using the RTK inhibitor lapatinib impacts on ERRalpha stability, while cells resistant to lapatinib treatment exhibit restored ERRalpha expression. We therefore mapped ERRalpha binding sites in parental (sensitive) cells (pSKBr3) as well as in lapatinib-resistant cells (LRSKBr3). ChIP-Seq analysis of ERRalpha binding profile in SKBr3 or BT-474 breast cancer cells.
2016-06-15 | E-GEOD-81651 | biostudies-arrayexpress
Project description:We previously demonstrated by genomic and bioinformatical approaches that human macrophage (MΦ) activation is best described by a spectrum model (Xue et al, Immunity, 2014). MΦ integrate exogenous input signals on transcriptional level in a unique fashion to generate specific functional programs, enabling the plasticity in disease-related pathophysiologies. Such versatile responsiveness requires fast changes of transcription mediated by transcriptional regulators (TRs) or epigenomic changes. To better understand the principles of this regulation during human MΦ activation, we assessed histone modifications including H3K4me1, H3K4me3, H3K27me3, and H3K27Ac by ChIP-sequencing allowing us to characterize the functional state of promoters (active, poised, repressed) and enhancers (active, inactive, intermediate). Using transcriptome data from our MΦ spectrum model, we generated a co-regulation network of all TRs. Next, we overlaid epigenomic information and transcriptional changes of major TRs over time onto the TR network. We observed that input signals like IFNγ or TNFα induce a specific network of TRs that are transcriptionally regulated themselves, the combination of regulated TRs changes over time with a boost of transcriptional regulation of dozens of TRs 4 to 12 hrs post input signal exposure, almost all TRs within the network show active promoters, even if the TR itself is not expressed, and similar results are obtained for enhancers with open or at least intermediated states. These findings strongly suggest that in MΦ, the TR-defined cellular â??switch panelâ?? is always accessible thereby allowing MΦ to quickly respond to the diverse input signal repertoire from the environment. Epigenetic analysis of promoter and enhancer sites in primary human macrophage subtypes and correlation to RNA-seq expression data
2016-02-28 | E-GEOD-66594 | biostudies-arrayexpress
Project description:Global Run-On has been performed in MLL2 F/F and FC/FC MEF cells. The aim of the experiment is to test how the lack of MLL2 affects nascent RNA transcription. Four samples were analyzed - 2 independent replicates. The experiments were performed using immortalized mouse embryonic fibroblasts (MEF) in which both MLL2 alleles were targeted by the loxp system (F/F cells). Tamoxifen treatment of the F/F cells for 24 hours results in the excision of both MLL2 alleles (FC/FC cells).
2016-04-13 | E-GEOD-73126 | biostudies-arrayexpress
Project description:Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock.M-BM- We have determined the underlyingM-BM- mechanisms by measuring nascent RNA transcription around the clock in mouse liver. Unbiased examination of eRNAs that cluster in specific circadian phasesM-BM- identified functional enhancers driven by distinct transcription factors (TFs). We further identify on a global scale the components of the TF cistromes that function to orchestrate circadian gene expression. Integrated genomicM-BM- analysesM-BM- also revealed novel mechanisms by which a single circadian factor controls opposing transcriptional phases. These findings shed new light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ. Nascent RNA transcripts in mouse liver were profiled at 8 time points of the 24 hour light-dark cycle. Static state mRNAs in WT and Rev-erbA -/- mice were profiled using microarray (GSE59460).
2014-11-21 | E-GEOD-59486 | biostudies-arrayexpress
Project description:Differential gene expression in mice liver after carbon tetrachloride and acetaminophen administration. Livers from control mice were compared with drug treated mice livers at different time points. Keywords: Time-course Mice (Mus musculus) belonging to control and carbon tetrachloride and acetaminophen-administered groups (n=4) were sacrificed. The livers were snap frozen in liquid nitrogen, and subsequently stored at -80ºC till further use. Liver samples were homogenized and total RNA was extracted with TRI reagent. 25 ug of total RNA was converted into labeled cDNA using CyScribe first strand cDNA labeling kit. The Cy5 and Cy3 labeled cDNAs were resuspended in Cyscribe Hyb buffer containing 10ug/ml sheared Salmon sperm DNA and 10ug/ml Yeast tRNA. The labeled samples were hybridized to the arrays and incubated for 16-18hrs at 42ºC. Fluorescent array images were collected for both Cy3 and Cy5 with molecular dynamics III scanner supported with ImageQuant v5.0. Image intensity data were extracted and analyzed with ArrayVision v8.0 analysis software. Background corrected data was LOWESS normalized and log ratios were calculated using Avadis v4. Further, mean log ratios were calculated for duplicate spots. Replicate experiments were carried out in dye swap manner for each time point.
2010-06-11 | E-GEOD-4874 | biostudies-arrayexpress
Project description:Alterations in chromatin accessibility independent of DNA methylation can affect cancer-related gene expression, but are often overlooked in conventional epigenomic profiling approaches. In this study, we describe a cost-effective and computationally simple assay called AcceSssIble to simultaneously interrogate DNA methylation and chromatin accessibility alterations in primary human clear cell renal cell carcinomas (ccRCC). Our study revealed significant perturbations to the ccRCC epigenome, and identified gene expression changes that were specifically attributed to the chromatin accessibility status whether or not DNA methylation was involved. Compared to commonly mutated genes in ccRCC, such as the von Hippel-Lindau (VHL) tumor suppressor, the genes identified by AcceSssIble comprised distinct pathways and more frequently underwent epigenetic changes, suggesting that genetic and epigenetic alterations could be independent events in ccRCC. Specifically, we found unique DNA methylation-independent promoter accessibility alterations in pathways mimicking VHL deficiency. Overall, this study provides a novel approach for identifying new epigenetic-based therapeutic targets, previously undetectable by DNA methylation studies alone, that may complement current genetic-based treatment strategies. Examination of 3 different histone modifications in 2 patient tumor and adjacent normal samples.
2016-03-15 | E-GEOD-75597 | biostudies-arrayexpress
Project description:We investigated the RNAPII and γH2AX occupancy genome wide by ChIP-Seq in MLL2 F/F and FC/FC80 MEF cells. We found that a week after MLL2 excision (FC/FC cells), a group of genes present higher levels of γH2AX and RNAPII near the TSS, as compared to the control (F/F cells). H3K4Me1, H3K4M2 and H3K4Me3 levels near the TSS were also studied. There is a total of 52 samples. 3 independent replicates for each experiment were performed. H3, H2AX and IgG ChIPs were used for normalisation or as controls.The experiments were performed using immortalised mouse embryonic fibroblasts (MEF) in which both MLL2 alleles were targeted by the loxp system (F/F cells). Tamoxifen treatment of the F/F cells for 24 hours results in the excision of both MLL2 alleles (FC/FC cells).
2016-04-13 | E-GEOD-73124 | biostudies-arrayexpress
Project description:We generated and sequenced ChIP libraries for the meiotic cohesin subunit REC8 and four histone modifications (H3K4me1, H3K4me2, H3K9me2 and H3K27me1) to investigate their relationships with meiotic chromosome architecture and recombination in Arabidopsis thaliana. REC8 and H3K9me2 ChIP-seq were performed using meiotic-stage floral buds from wild type (Col-0) and non-CG DNA methylation/H3K9me2 pathway mutant (kyp/suvh4 suvh5 suvh6 or cmt3) plants to examine the role of heterochromatin assembly in meiotic cohesin distribution.
2020-01-21 | E-MTAB-7370 | biostudies-arrayexpress
Project description:The development of therapeutic anticancer vaccines calls for the identification of tumor-specific antigens (TSAs). Though a combination of four cutting-edge proteogenomic approaches, we performed a deep exploration of the MHC-I presented peptides (MAPs) of 19 acute myeloid leukemia (AML) patients and identified various TSAs that could serve for the design of an anti-AML vaccine.
2021-03-19 | PXD018542 | Pride
Project description:Background: Epigenetic modification is a hallmark of cancer cells achieved through altered patterns of DNA methylation, histone modifications and nucleosome positions. These events have only been described in detail at gene promoters. Results: Here, we integrate multiple epigenome-wide maps to evaluate the scope of global epigenetic reprogramming in cancer cells at enhancers and insulators. Using high-resolution simultaneous mapping of global DNA methylation and nucleosome positions within individual DNA strands (NOMe-Seq), we observe a reorganization of the DNA methylome coupled with simultaneous modulation of nucleosome depleted regions (NDRs) at distal regulatory elements in cancer cells. We show that while NDRs are preferentially found at enhancers in normal breast and prostate epithelial cells, there are fewer NDRs coupled with increased DNA methylation detected at enhancersin cancer cells. Our data suggests that the acquisition of a nucleosome is key to DNA hypermethylation susceptibility and contributes to epigenetic silencing of enhancers in cancer, which can notably occur without loss of H3K4me1. Further we observe that NDRs are not necessary for peripheral phasing of adjacent nucleosomes, contrary to the common dogma, and show that nucleosomes remain organized and phased, even in the absence of a NDR as an anchor. Finally we observe the potential for transcription factors (TF) to organize NDRs genome-wide; all TF-binding sites are strongly hypomethylated and some show extensive peripheral nucleosome phasing. Conclusion: Together our findings suggest that, in addition to epigenetic alterations to promoter regions in cancer, there is substantial disruption to the distal regulatory architecture that provides an additional layer of epigenetic plasticity in malignancy. NOMe-seq, ChIP-seq for 5 marks and input control for breast normal (HMEC), breast cancer (MCF7), prostate normal (PrEC) and prostate cancer (PC3) cell lines
2014-06-04 | E-GEOD-57498 | biostudies-arrayexpress