Cancer cells with genetic disruption of DNA methyltransferases
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ABSTRACT:
PROVIDER: PRJNA360114 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Maximizing DNA methyltransferase (DNMT’s) inhibition for cancer therapy requires defining the roles and interactions between these enzymes for maintaining the widespread DNA methylation abnormalities in cancer. Combining genetic and shRNA depletion in colon and other cancer cells reveals that DNMT1 is extremely dominant in this maintenance, with DNMT’s 3A and 3B playing minor roles, at all genomic loci including promoters and enhancers. Reducing DNMT1 below a deep threshold level, especially at promoters, is required for reversing abnormal DNA methylation and re-expressing key tumor suppressor genes. Current DNMT inhibitors (DNMTis) are challenged, at tolerable patient doses, for achieving such reductions. We introduce a new approach in which reducing levels of the DNMT targeting protein, UHRF1, complements low DNMTi doses to DNA demethylate and reactivate expression of such genes.
2017-01-13 | GSE77247 | GEO
Project description:Maximizing DNA methyltransferase (DNMT’s) inhibition for cancer therapy requires defining the roles and interactions between these enzymes for maintaining the widespread DNA methylation abnormalities in cancer. Combining genetic and shRNA depletion in colon and other cancer cells reveals that DNMT1 is extremely dominant in this maintenance, with DNMT’s 3A and 3B playing minor roles, at all genomic loci including promoters and enhancers. Reducing DNMT1 below a deep threshold level, especially at promoters, is required for reversing abnormal DNA methylation and re-expressing key tumor suppressor genes. Current DNMT inhibitors (DNMTis) are challenged, at tolerable patient doses, for achieving such reductions. We introduce a new approach in which reducing levels of the DNMT targeting protein, UHRF1, complements low DNMTi doses to DNA demethylate and reactivate expression of such genes.
2017-01-13 | GSE93142 | GEO
Project description:Maximizing DNA methyltransferase (DNMT’s) inhibition for cancer therapy requires defining the roles and interactions between these enzymes for maintaining the widespread DNA methylation abnormalities in cancer. Combining genetic and shRNA depletion in colon and other cancer cells reveals that DNMT1 is extremely dominant in this maintenance, with DNMT’s 3A and 3B playing minor roles, at all genomic loci including promoters and enhancers. Reducing DNMT1 below a deep threshold level, especially at promoters, is required for reversing abnormal DNA methylation and re-expressing key tumor suppressor genes. Current DNMT inhibitors (DNMTis) are challenged, at tolerable patient doses, for achieving such reductions. We introduce a new approach in which reducing levels of the DNMT targeting protein, UHRF1, complements low DNMTi doses to DNA demethylate and reactivate expression of such genes.
2017-01-13 | GSE93135 | GEO
Project description:Ctcf heterozygous knockout mice are susceptible to neoplasia in a broad range of tissues, including lymphoma, endometrial cancer, and non-small cell lung cancer. Retention of the wild type Ctcf allele in these tumors establishes CTCF as a haploinsufficient tumor suppressor gene. Both human tumors and normal murine tissues with CTCF disruption are characterized by genome-wide differences in DNA methylation relative to CTCF wild type tissues, indicating even modest disruption of CTCF broadly destabilizes DNA methylation in vivo. This cross species functional analysis identifies CTCF as a commonly mutated tumor suppressor gene and establishes a central role for DNA methylation stability in tumor suppression. RRBS sequencing of transgenic Ctcf heterozygous mice and wild-type litter mate whole lung tissue.
2014-07-30 | E-GEOD-48975 | biostudies-arrayexpress
Project description:Genomic context sensitizes regulatory elements to genetic disruption [DNA]
| PRJNA1009155 | ENA
Project description:Ctcf heterozygous knockout mice are susceptible to neoplasia in a broad range of tissues, including lymphoma, endometrial cancer, and non-small cell lung cancer. Retention of the wild type Ctcf allele in these tumors establishes CTCF as a haploinsufficient tumor suppressor gene. Both human tumors and normal murine tissues with CTCF disruption are characterized by genome-wide differences in DNA methylation relative to CTCF wild type tissues, indicating even modest disruption of CTCF broadly destabilizes DNA methylation in vivo. This cross species functional analysis identifies CTCF as a commonly mutated tumor suppressor gene and establishes a central role for DNA methylation stability in tumor suppression.
2014-07-30 | GSE48975 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-01-13 | GSE93136 | GEO
Project description:DNA methylation profiling of cancer cells with genetic disruption of DNA methyltransferases
| PRJNA309847 | ENA
Project description:Genome wide DNA methylation profiling of normal and tumor prostate samples, as well as cultured primary prostate cells overexpressing DNA Methyltransferases (DNMTs) and EZH2 Candidate gene based studies have identified a handful of aberrant CpG DNA methylation events in prostate cancer. However, DNA methylation profiles have not been compared on a large scale between prostate tumor and normal prostate, and the mechanisms behind these alterations are unknown. In this study, we quantitatively profiled 95 primary prostate tumors and 86 healthy prostate tissue samples for their DNA methylation levels at 26,333 CpGs representing 14,104 gene promoters by using the Illumina HumanMethylation27 platform. A 2-class Significance Analysis of this dataset revealed 5,912 CpG sites with increased DNA methylation and 2,151 CpG sites with decreased DNA methylation in tumors (FDR < 0.8%). Prediction Analysis of this dataset identified 87 CpGs that are the most predictive diagnostic methylation biomarkers of prostate cancer. By integrating available clinical follow-up data, we also identified 69 prognostic DNA methylation alterations that correlate with biochemical recurrence of the tumor. To identify the mechanisms responsible for these genome-wide DNA methylation alterations, we measured the gene expression levels of several DNA methyltransferases (DNMTs) and their interacting proteins by TaqMan qPCR and observed increased expression of DNMT3A2, DNMT3B, and EZH2 in tumors. Subsequent transient transfection assays in cultured primary prostate cells revealed that DNMT3B1 and DNMT3B2 overexpression resulted in increased methylation of a substantial subset of CpG sites that also showed tumor-specific increased methylation. Bisulfite converted DNA from 193 samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2. The tissue samples (first 181) and the cultured cell samples (last 12) were normalized independently.
2011-04-19 | E-GEOD-26126 | biostudies-arrayexpress
Project description:Mouse embryos acquire global DNA methylation of their genome during implantation. However the exact roles of DNA methyltransferases (DNMTs) in embryognesis have not been studied comprehensively. Here we systematically analyze the consequences of genetic inactivation of Dnmt1, Dnmt3a and Dnmt3b on the methylome and transcriptome of mouse embryos and fibroblasts.
2020-05-20 | GSE130735 | GEO