|
| Status |
Public on Sep 13, 2011 |
| Title |
Epigenetic profiling of hematopoietic stem cells and leukemia stem cells |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations that involve the Mixed Lineage Leukemia (MLL) gene. We identified the MLL-fusion targets in a murine MLL-AF9 leukemia model, and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3 and H3K36me3. Histone methylation patterns are highly abnormal on MLL-AF9 fusion target loci, defining a distinct epigenetic lesion involving H3K79. Conditional inactivation of Dot1l leads to specific down-regulation of direct MLL-AF9 targets and an MLL-translocation associated gene expression signature, while global transcription levels remain largely unaffected. This correlated with a greater sensitivity of leukemic blasts towards loss of Dot1l compared to normal hematopoietic cells. Development of in vivo leukemia was absolutely dependent on Dot1l.
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| |
|
| Overall design |
Chromatin immunoprecipitation followed by Solexa sequencing for H3K4me3, H3K27me3, H3K36me3, H3K79me2 and biotinylated MLL-AF9 in HSC, GMP and LSC.
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| |
|
| Contributor(s) |
Sinha A, Zhu N, Armstrong S |
| Citation(s) |
21741597 |
| |
| Submission date |
May 06, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Amit Sinha |
| E-mail(s) |
amit.sinha@childrens.harvard.edu
|
| Phone |
617-582-7579
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Pediatric Oncology
|
| Lab |
Armstrong Lab
|
| Street address |
44 Binney St
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02135 |
| Country |
USA |
| |
|
| Platforms (3) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (15)
|
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| Relations |
| SRA |
SRP006724 |
| BioProject |
PRJNA140445 |
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