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Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis

ABSTRACT: Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis

PROVIDER: PRJNA290163 | ENA |

REPOSITORIES: ENA

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Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (RRBS)

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.

2016-01-11 | E-GEOD-71039 | biostudies-arrayexpress

Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (RRBS)

2016-01-11 | GSE71039 | GEO

Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (expression)

Project description:Here, we analyzed global gene expression changes that were associated with over expression of Dnmt3b in MLL-AF9 induced leukemias using the Affymetrix microarray platform. Changes in global gene expression were determined with Affymetrix microarrays in MLL-AF9 induced leukemias over expressing Dnmt3b.

2016-01-11 | E-GEOD-71040 | biostudies-arrayexpress

Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (expression)

Project description:Here, we analyzed global gene expression changes that were associated with over expression of Dnmt3b in MLL-AF9 induced leukemias using the Affymetrix microarray platform.

2016-01-11 | GSE71040 | GEO

Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis

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

2016-01-11 | E-GEOD-71041 | biostudies-arrayexpress

Mus musculus

Project description:Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (RRBS)

| PRJNA290166 | ENA

Mus musculus

Project description:Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (expression)

| PRJNA290165 | ENA

Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-01-11 | GSE71041 | GEO

Targets and genomic constraints of ectopic Dnmt3b expression

Project description:Targets and genomic constraints of ectopic Dnmt3b expression

| PRJNA483553 | ENA

Targets and genomic constraints of ectopic Dnmt3b expression

Project description:DNA methylation plays an essential role in mammalian genomes, hence DNA methyltransferase expression is tightly controlled. Deregulation of the de novo enzyme DNMT3B is frequently observed in many diseases, yet little is known about its ectopic genomic targets. Here we used an inducible transgenic mouse model to identify rules delineating abnormal DNMT3B targeting and explore the constraints of its activity across different cell types. Our results explain the preferential susceptibility of certain CpGs to aberrant methylation and point to transcriptional state and the associated chromatin landscape as the strongest predictors. Although DNA methylation and H3K27me3 are usually antagonistic at CpG islands, H3K27me3 can transiently co-occur with DNMT3B-induced DNA methylation and its depletion has minimal affect on ectopic methylation targets or levels in mouse embryonic fibroblasts. Our multilayered genome-wide data combined with ultra-deep locus-specific bisulfite sequencing suggest a hit-and-run model that induces hypermethylation and provides insights for interpreting the cancer methylome.

2018-11-20 | GSE117909 | GEO

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