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| Status |
Public on Jan 11, 2016 |
| Title |
Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (RRBS) |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
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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| Contributor(s) |
Rohde C, Schulze I, Müller-Tidow C |
| Citation(s) |
26729896 |
| Submission date |
Jul 17, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Christian Rohde |
| E-mail(s) |
christian.rohde@uni-heidelberg.de
|
| Organization name |
Heidelberg University
|
| Lab |
Molecular Hematology and Oncology
|
| Street address |
Im Neuenheimer Feld 410
|
| City |
Heidelberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
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| Platforms (1) |
| GPL16173 |
Illumina HiScanSQ (Mus musculus) |
|
| Samples (10)
|
| GSM1825961 |
RRBS cMyc-Bcl2 leukemic spleen cells cMyc-Bcl2-13439 |
| GSM1825962 |
RRBS cMyc-Bcl2 leukemic spleen cells Dnmt3b-knockin cMyc-Bcl2-13473 |
| GSM1825963 |
RRBS cMyc-Bcl2 leukemic spleen cells cMyc-Bcl2-13477 |
| GSM1825964 |
RRBS cMyc-Bcl2 leukemic spleen cells Dnmt3b-knockin cMyc-Bcl2-13953 |
| GSM1825965 |
RRBS MLL-AF9 c-kit+ leukemic spleen cells MLL-AF9-73-0 |
| GSM1825966 |
RRBS MLL-AF9 c-kit+ leukemic spleen cells MLL-AF9-75-0 |
| GSM1825967 |
RRBS MLL-AF9 c-kit+ leukemic spleen cells MLL-AF9-79-0 |
| GSM1825968 |
RRBS MLL-AF9 c-kit+ leukemic spleen cells Dnmt3b-knockin MLL-AF9-81-0 |
| GSM1825969 |
RRBS MLL-AF9 c-kit+ leukemic spleen cells Dnmt3b-knockin MLL-AF9-83-0 |
| GSM1825970 |
RRBS MLL-AF9 c-kit+ leukemic spleen cells Dnmt3b-knockin MLL-AF9-85-0 |
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| This SubSeries is part of SuperSeries: |
| GSE71041 |
Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis |
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| Relations |
| BioProject |
PRJNA290166 |
| SRA |
SRP061268 |
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