Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA136305 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR094793.fastq.gz | Fastqsanger.gz | |||
| SRR094794.fastq.gz | Fastqsanger.gz | |||
| SRR094795.fastq.gz | Fastqsanger.gz | |||
| SRR094796.fastq.gz | Fastqsanger.gz | |||
| SRR094797.fastq.gz | Fastqsanger.gz |
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Project description:The methylation status of colon epithelial cells was profiled in wild type mice and mice expressing a Dnmt3b transgene. Genome-scale methylation profiles were generated using reduced representation bisulfite sequencing (RRBS), with CpG methylation scored by promoter and also summarized by gene. Dnmt3b expression is associated with a strong increase in de novo methylation of a discrete subset of "methylation sensitive" genes which show a strong concordance with genes methylated in human colon cancer. These results, together with further analysis, indicate that colon epithelial cell methylation in the Dnmt3b mouse model predicts DNA methylation of human colon cancer with high confidence.
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Project description:The de novo DNA methyltransferases Dnmt3a and Dnmt3b are of crucial importance in hematopoietic stem cells, and Dnmt3b has recently been shown to play a role in genic methylation. Forced Dnmt3b expression induced widespread DNA hypermethylation in myc-bcl2 induced leukemias, especially at promoters and gene bodies of stem cell-related genes. MLL-AF9 induced leukemogenesis showed much less pronounced DNA hypermethylation upon Dnmt3b expression. Nonetheless, leukemogenesis was delayed in both models with a shared core set of DNA hypermethylated regions and suppression of stem cell-related genes. Our findings indicate a critical role for Dnmt3b-mediated DNA methylation in leukemia development and maintenance of LSC function. To investigate how Dnmt3b-mediated DNA methylation affects leukemogenesis, we analyzed leukemia development under conditions of high and physiological methylation levels in a tetracycline-inducible knockin mouse model. High expression of Dnmt3b slowed leukemia development in serial transplantations and impaired leukemia stem cell (LSC) function.
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Project description:Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (expression)
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