Project description:This SuperSeries is composed of the following subset Series: GSE31864: Epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells GSE31865: Global methylation in normal and malignant urothelial cells Refer to individual Series
Project description:To gain a more depth knowledge of repressive epigenetic gene regulation in UCC, we have profiled H3K9m3 and H3K27m3 in normal and malignant urothelial cells. We matched these profiles to those 5-methylcytosine and gene expression. We hypothesized that differences represent pro-carcinogenic events within the urothelium. We identified a panel of genes with cancer specific epigenetic mediated aberrant expression. Two repressive histone modifications (H3K9m3 and H3K27m3) , cytosine methylation and gene expression were compared between normal human urothelial cell line (NHU) and malignant urothelial cells (EJ and RT112).
Project description:Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells [ChIP-Seq data]
Project description:We profiled two repressive histone modifications (H3K9m3 and H3K27m3) using ChIP-Seq in normal urothelial cells and cell lines representing non-invasive and invasive tumors. Two bladder cancer cell lines (RT112 and EJ/T24 from ATCC) and normal human urothelial (NHU) cells were treated according to standard ChIP-Seq protocols using antibodies against the histone modifications H3K9m3 and H3K27m3 (from Millipore). The sequencing reads were mapped against the human genome (GRCh37/hg19).
Project description:We profiled two repressive histone modifications (H3K9m3 and H3K27m3) using ChIP-Seq in normal urothelial cells and cell lines representing non-invasive and invasive tumors.
Project description:DNA and Histone-3 Lysine 27 methylation typically function as repressive modifications and operate within distinct genomic compartments. In mammals, the majority of the genome is kept in a DNA methylated state, whereas the Polycomb Repressive Complexes regulate the unmethylated CpG-rich promoters of developmental genes. In contrast to this general framework, the extraembryonic lineages display non-canonical, globally intermediate DNA methylation levels that includes disruption of local Polycomb domains. To better understand this unusual landscape’s molecular properties, we genetically and chemically perturbed major epigenetic pathways in mouse Trophoblast Stem Cells (TSCs). We find that the extraembryonic epigenome reflects ongoing and dynamic de novo methyltransferase recruitment, which is continuously antagonized by Polycomb to maintain intermediate, locally disordered methylation. Despite its disorganized molecular appearance, our data point to a highly controlled equilibrium between counteracting repressors within extraembryonic cells, one that can seemingly persist indefinitely without bistable features typically seen for embryonic forms of epigenetic regulation.
Project description:DNA and Histone-3 Lysine 27 methylation typically function as repressive modifications and operate within distinct genomic compartments. In mammals, the majority of the genome is kept in a DNA methylated state, whereas the Polycomb Repressive Complexes regulate the unmethylated CpG-rich promoters of developmental genes. In contrast to this general framework, the extraembryonic lineages display non-canonical, globally intermediate DNA methylation levels that includes disruption of local Polycomb domains. To better understand this unusual landscape’s molecular properties, we genetically and chemically perturbed major epigenetic pathways in mouse Trophoblast Stem Cells (TSCs). We find that the extraembryonic epigenome reflects ongoing and dynamic de novo methyltransferase recruitment, which is continuously antagonized by Polycomb to maintain intermediate, locally disordered methylation. Despite its disorganized molecular appearance, our data point to a highly controlled equilibrium between counteracting repressors within extraembryonic cells, one that can seemingly persist indefinitely without bistable features typically seen for embryonic forms of epigenetic regulation. Dataset 1: EED co-immunoprecipitation of wild type mouse trophoblast stem cells (TSCs) and Eed knockout TSCs as control, with 3 biological replicates per condition.
Project description:DECREASE IN DNA METHYLATION 1 (DDM1) is the chromatin remodeling factor that has been genetically identified in Arabidopsis thaliana as a factor involved in the maintenance of repressive epigenomic modifications over transposons. In this study, we performed crosslinking mass spectrometry and biochemical analysis using reconstituted nucleosome to understand the chromatin remodeling activity of DDM1. We found that the unique C-terminal tail of heterochromain-specific H2A.W variant binds to DDM1. This result suggest that DDM1 functions with specific histone variants for the maintenance of repressive modifications and epigenetic regulation of transposon activity.
Project description:Genome wide DNA methylation profiling of normal and upper-tract urothelial carcinomas tissues. The Illumina Infinium EPIC arrays was used to obtain DNA methylation profiles across approximately 866,091 probes. Samples included 35 upper-tract urothelial carcinomas samples and 8 adjacent normal tissues
