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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Altered epigenetic programming links intestinal inflammation to colon cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Guenter Raddatz

PROVIDER: E-GEOD-57569 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Chronic inflammation induces a novel epigenetic program that is conserved in intestinal adenomas and in colorectal cancer.

Abu-Remaileh Monther M Bender Sebastian S Raddatz Günter G Ansari Ihab I Cohen Daphne D Gutekunst Julian J Musch Tanja T Linhart Heinz H Breiling Achim A Pikarsky Eli E Bergman Yehudit Y Lyko Frank F

Cancer research 20150325 10

Chronic inflammation represents a major risk factor for tumor formation, but the underlying mechanisms have remained largely unknown. Epigenetic mechanisms can record the effects of environmental challenges on the genome level and could therefore play an important role in the pathogenesis of inflammation-associated tumors. Using single-base methylation maps and transcriptome analyses of a colitis-induced mouse colon cancer model, we identified a novel epigenetic program that is characterized by ...[more]

PMID: 25808873

Similar Datasets

Altered epigenetic programming links intestinal inflammation to colon cancer (Bisulfite-seq)

Project description:This study uses whole-genome bisulfite sequencing to characterize the methylomes of the AOM/DSS mouse model at single-base resolution. In this model, mice are treated with dextran sodium sulfate (DSS) to induce colitis. When this treatment is preceded by injections of the weak carcinogen azoxymethane (AOM) the mice develop intestinal tumors. Our results identify hypermethylated DMVs as a prominent feature of the colitis methylome that is conserved in intestinal adenocarcinomas. Further analyses reveal a subset of DMV-associated genes, expressed in normal intestinal epithelial cells, that were silenced and hypermethylated in inflamed and cancerous intestinal cells. Together, these findings provide strong support for the hypothesis that inflammatory signals induce a higher risk for cancer development by manipulating the epigenome. . Whole genome methylation analysis of M. musculus. Three conditions were sequenced analyzed, the first is an untreated control, the second corresponds to inflammation, the third to cancer induced by inflammation. All three conditions were analyzed using three replicates.

2015-06-17 | E-GEOD-57527 | biostudies-arrayexpress

Altered epigenetic programming links intestinal inflammation to colon cancer (RNA-seq)

Project description:This study uses whole-transcriptome sequencing to characterize the transcriptomes of the AOM/DSS mouse model. In this model, mice are treated with dextran sodium sulfate (DSS) to induce colitis. When this treatment is preceded by injections of the weak carcinogen azoxymethane (AOM) the mice develop intestinal tumors. Our results identify sets of differentially expressed genes which are correlated with methylation changes of the corresponding genes. Whole transcriptome analysis of Mus musculus. Three conditions were sequenced and analyzed, the first is an untreated control, the second corresponds to inflammation induced by applying DSS, the third to cancer induced by inflammation and application of AOM. The control condition as well as the AOM-induced cancer condition were analyzed using three replicates, the second condition using 4 replicates.

2015-06-17 | E-GEOD-57533 | biostudies-arrayexpress

Whole genome bisulfite sequencing of Entamoeba histolytica

Project description:Up until now, the existence of Dnmt2-mediated DNA methylation has mostly been supported by focal analyses in organisms that contain Dnmt2, but no Dnmt1 or Dnmt3 DNA methyltransferase. In these organisms, several independent studies have also provided support for a biologically important function of Dnmt2-dependent DNA methylation. For example, Dnmt2-dependent methylation in Entamoeba histolytica, the causative agent of amebic dysentery, has been connected to the parasite s virulence. However, global DNA methylation levels in Entamoeba have been found to be very low. In addition, no specific features, such as CpG-specificity and specificity for certain genetic subcompartments have been described. This distinguishes Dnmt2-dependent methylation patterns from all other known methylomes and has raised questions about the validity of the underlying results. We have used whole-genome bisulfite sequencing for an unbiased characterization of the Entamoeba histolytica methylome at single-base resolution in a E.histolytica strain HM-1:IMSS devoid of significant level of EhDnmt2 (Ehmeth) expression. Paired-end BS-sequencing was performed on an Illumina Genome Analyzer with read lengths of 105 base pairs and an average insert size of 200 bp.

2011-08-10 | E-GEOD-31295 | biostudies-arrayexpress

Dnmt2-dependent methylomes lack biologically relevant DNA methylation patterns [Schistosoma mansoni]

Project description:Dnmt2 is a widely conserved protein, which is closely related to eukaryotic DNA methyltransferases. However, Dnmt2 shows a robust tRNA methyltransferase activity and only limited activity towards DNA. Interestingly, a recent study has provided evidence for a biologically important function of Dnmt2-dependent DNA methylation in the blood fluke Schistosoma mansoni, which seemed to contradict the weak activity of the enzyme in other organisms. We now used whole-genome bisulfite sequencing to comprehensively analyze the methylome of adult worms and could not detect any evidence for biologically relevant DNA methylation patterns. We also characterized the methylome of Drosophila melanogaster embryos and did not find any evidence for DNA methylation. Unconverted cytosine residues were detectable only at very low levels and shared many attributes with bisulfite deamination artifacts. Our results thus strongly argue against a DNA methyltransferase activity of Dnmt2 and suggest that Dnmt2-dependent phenotypes are caused by reduced tRNA methylation. Whole genome methylation analysis of S. mansoni. One sample was analyzed, containing DNA from adult male worms.

2013-05-06 | E-GEOD-39997 | biostudies-arrayexpress

Tet1 and Tet2 mediate epigenetic regulation of developmental genes by protecting DNA methylation canyons against hypermethylation [Bisulfite-Seq]

Project description:This study uses whole methylome sequencing to characterize the methylomes of mouse embryonic fibroblasts (MEF's). Two conditions were analyzed, MEF cells with intact TET1/TET2 enzymes (WT) and MEF cells with TET1/TET2 knocked out (DKO). Our results identify sets of differentially methylated genes which are correlated with TET1/TET2 induced expression changes of the corresponding genes. Whole methylome analysis of M. musculus MEF cells. Two conditions were sequenced and analyzed, the first is wild type (WT), the second (DKO) corresponds to knock-out of TET1 and TET2 enzymes.

2015-12-07 | E-GEOD-58610 | biostudies-arrayexpress

Tet1 and Tet2 mediate epigenetic regulation of developmental genes by protecting DNA methylation canyons against hypermethylation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-12-07 | E-GEOD-58611 | biostudies-arrayexpress

Dnmt3a protects active chromosome domains against cancer-associated hypomethylation

Project description:The results of the study uncover conserved features of cancer methylomes and provide a mechanistic explanation for the tumor-promoting effects of Dnmt3a mutations. Whole genome methylation analysis of Mus musculus. Five samples were analyzed, one control sample containing normal healthy lung tissue, two samples containing big (WTB) or small (WTS) Dnmt3a WT tumors, two samples containing big (KOB) or small (KOS) Dnmt3a knock-out tumors

2013-01-22 | E-GEOD-38651 | biostudies-arrayexpress

Project description:Altered DNA methylation patterns represent an attractive mechanism for the phenotypic changes associated with human aging. Several studies have described age-related methylation changes to various extents, but their functional significance has remained largely unclear. We have now used an integrated methylome and transcriptome sequencing approach to characterize age-related methylation changes in the human epidermis and to analyze their impact on gene expression. Our results show limited and localized methylation differences between young and old methylomes at single-base resolution. Similarly, the comparison of transcriptomes from young and old samples revealed a highly defined set of differentially expressed genes with functional annotations in skin homeostasis. Further data analysis showed a robust correlation between age-related promoter hypermethylation and gene silencing, particularly at promoters that were pre-marked with stem cell-specific chromatin features. In addition, we also observed age-related methylation changes at transcription factor binding sites, with a significant enrichment of stem cell regulatory networks. Our results provide a high-resolution analysis of age-related methylation changes and suggest that they result in highly defined alterations in the transcriptional programme of the human epidermis. Interestingly, several of our findings can be interpreted to reflect epigenetic changes in aging stem cells, thus supporting a critical role of stem cells in human aging. Whole genome methylation analysis of H. sapiens. Two samples were analyzed, one sample containing DNA from young, one sample containing DNA from old human skin.

2013-12-20 | E-GEOD-46450 | biostudies-arrayexpress

Genome-scale methylome analysis of the desert locust, Schistocerca gregaria

Project description:DNA methylation is a widely conserved epigenetic modification that is established and maintained by the cooperative activity of DNA methyltransferases. While the complement of DNA methyltransferase genes can vary substantially between animal species, whole-genome methylation analyses have suggested that major features of animal methylomes are widely conserved. We have now used genome-scale bisulfite sequencing to analyze the methylome of the desert locust, Schistocerca gregaria, which represents an economically important pest with a high degree of phenotypic plasticity. Interestingly, in this system, DNA methylation appears to be both established and maintained by Dnmt1 methyltransferases, which distinguishes locusts from most other known organisms. Our results indicate that the S. gregaria methylome shares preferential methylation of CpG dinucleotides and exons with other animal methylomes. In contrast to other invertebrates, however, overall methylation levels were substantially higher and a significant fraction of transposons was methylated. Additionally, genes were densely methylated in a pronounced bimodal pattern, suggesting a role for DNA methylation in the regulation of locust gene expression. Altogether, our results uncover a unique pattern of genome methylation in locusts and also suggest that animal methylomes may be more diverse than previously thought. Whole exome methylation analysis of S. gregaria. Two samples were analyzed, one sample containing DNA from brain, one sample containing DNA from MTG. To date, there exists no sequenced genome of Schistocerca gregaria; thus, we could only map the data against an EST database (Locust2 EST project) representing the coding part of the genome.

2013-05-03 | E-GEOD-41214 | biostudies-arrayexpress

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-12-20 | E-GEOD-46487 | biostudies-arrayexpress

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