Project description:Epigenomics is developing a colon cancer screening assay based on differential methylation of specific CpG sites for the detection of early stage disease. A genome-wide methylation analysis and oligonucleotide array study using DNA from various stages of colon cancer and normal tissue have been completed to obtain candidate CpG markers. Based on results obtained in the above studies, Epigenomics has moved to the final stages of feasibility with a specific, highly sensitive real-time marker assay that is able to detect colon cancer DNA in blood plasma.
Project description:We show developmental-series transcriptome, methylome, and metabolome to reveal extensive epigenetic reprogramming during black raspberry (Rubus occidentalis) fruit ripening. Multi-omics integration reveals coordinated anthocyanin accumulation parallels expression of biosynthetic and regulatory genes within coherent networks. Our study highlights both genome-wide and locus-specific epigenetic reprogramming and demonstrates a coordinated interplay between DNA methylation and transcriptional regulation during black raspberry fruit ripening.
Project description:DNA methylation is a key epigenetic modification regulating genome organization, stability, and gene expression. Stable DNA methylation critically relies on methyl groups provided through folate-mediated one-carbon (C1) metabolism, yet the origin and regulation of C1 supply remain elusive. Here we demonstrate that photorespiration serves as a major C1 source for DNA methylation in Arabidopsis. We show that C1 from formate, a photorespiratory byproduct, is incorporated into 5-methyl-cytosine via the reductive cytosolic folate pathway. This occurs predominantly during the day, negatively regulating serine utilization as alternative C1 source. Consequently, suppression of photorespiration under elevated CO₂ levels alters the DNA methylation landscape, an effect exacerbated when regulation of C1 metabolism by the formate-dependent pathway is impaired. Thus, our findings link the fundamental metabolic process of photorespiration to epigenetic stability, highlighting how rising atmospheric CO₂ levels can induce DNA methylation changes.
Project description:Histone modification H3K9me2 is associated heterochromatin and gene silencing, but the relationship between DNA methylation and H9K9me2 haven’t been checked in a genome-wide scale. This dataset was generated to compare with genome-wide DNA methylation data.
Project description:This SuperSeries is composed of the following subset Series: GSE34655: Genome-wide profiling of DNA methylation in two Arabidopsis ecotypes and their reciprocal hybrids - mRNA-seq GSE34656: Genome-wide profiling of DNA methylation in two Arabidopsis ecotypes and their reciprocal hybrids - small RNA-seq GSE34657: Genome-wide profiling of DNA methylation in two Arabidopsis ecotypes and their reciprocal hybrids - Bisulfite-seq Refer to individual Series
Project description:DNA methylation is an essential epigenetic mark that is required for normal development. Knockout of the DNA methyltransferase enzymes in the mouse hematopoietic compartment reveals that methylation is critical for hematopoietic differentiation. To better understand the role of DNA methylation in hematopoiesis, we characterized genome-wide DNA methylation in primary mouse hematopoietic stem cells (HSC), common myeloid progenitors (CMP), and erythroblasts (ERY). Methyl Binding Domain protein 2 (MBD) enrichment of DNA followed by massively-parallel sequencing (MBD-Seq) was used to map genome-wide DNA methylation. Globally, DNA methylation was most abundant in HSC, with a 40% reduction in CMP, and 67% reduction in ERY. Only 3% of peaks arise during differentiation demonstrating a genome-wide decline in DNA methylation during erythroid development. Analysis of genomic features revealed that 98% of promoter CpG islands are hypomethylated, while 20-25% of non-promoter CpG islands are methylated. Proximal promoter sequences of expressed genes are hypomethylated in all cell types, while gene body methylation positively correlates with gene expression in HSC and CMP. Elevated genome-wide DNA methylation in HSC and the positive association between methylation and gene expression demonstrates that DNA methylation is a mark of cellular plasticity in HSC. Utilizing de novo motif discovery we identified overrepresented transcription factor consensus binding motifs in methylated sequences. Motifs for several ETS transcription factors, including GABPalpha and ELF1 are overrepresented in methylated regions. Our genome-wide survey demonstrates that DNA methylation is markedly altered during myeloid differentiation and identifies critical regions of the genome and transcription factor programs that contribute to hematopoiesis. Examination of changes in methylation profiles during hematopoietic stem cell differentiation
Project description:Naive pluripotent epiblast cells of the preimplantation murine embryo and their in vitro counterpart, embryonic stem (ES) cells, have the capacity to give rise to all cells of the adult. Such developmental plasticity is associated with global genome hypomethylation. It is unclear whether genome methylation is dynamically regulated only via differential expression of DNA methyltransferases (DNMTs) and Ten-eleven Translocation (TET) enzymes, which oxidase methylated DNA. Here we show that LIF/Stat3 signalling induces genomic hypomethylation via metabolic reconfiguration. In Stat3-/- ES cells we observed decreased alpha-ketoglutarate (ɑKG) production from reductive Glutamine metabolism, leading to decreased TET activity, increased Dnmt3a/b expression and to a global increase in DNA methylation. Notably, genome methylation is dynamically controlled by simply modulating αKG availability, mitochondrial activity or Stat3 activation in mitochondria, indicating effective crosstalk between metabolism and the epigenome. Stat3-/- ES cells also show increased methylation at Imprinting Control Regions accompanied with differential expression of >50% of imprinted genes. Single-cell transcriptome analysis of Stat3-/- embryos confirmed dysregulated expression of Dnmt3a/b, Tet2, and imprinted genes in vivo. Our results reveal that the LIF/Stat3 signal bridges the metabolic and epigenetic profiles of naive pluripotent cells, ultimately controlling genome methylation and imprinted gene expression. Several imprinted genes regulate cell proliferation and are often misregulated in tumors. Moreover, a wide range of cancers display Stat3-overactivation, raising the possibility that the molecular module we described here is exploited under pathological conditions.
Project description:This SuperSeries is composed of the following subset Series: GSE33226: Genome wide DNA methylation analysis of leukemia and reprogrammed leukemia cells (gene expression) GSE33230: Genome wide DNA methylation analysis of leukemia and reprogrammed leukemia cells (sequencing) Refer to individual Series
Project description:Estrogen receptor beta (ERβ) is a ligand inducible transcription factor regulating gene expression in response to the female sex hormone estrogen. Previously, we found that ERβ deficiency results in changes in DNA methylation patterns at two gene promoters, implicating an involvement of ERβ in DNA methylation. In this study, we set out to explore this involvement on a genome-wide level, and to investigate the underlying mechanisms of this function. Using reduced representation bisulfite sequencing (RRBS), we compared genome-wide DNA methylation in mouse embryonic fibroblasts (MEFs) derived from wildtype (wt) and ERβ knock-out (βerko) mice, and identified around 8000 differentially methylated positions (DMPs). This suggests that ERβ is involved in regulating DNA methylation at specific sites in the genome. Genome-wide DNA methylation was analysed in MEFs derived from wildtype and ERbeta null mice by educed representation bisulfite sequencing (RRBS) on an Illumina Genome Analyser IIx platform.